Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
In Vivo
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
In Vivo

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleExperimental Studies

Chlorogenic Acid Induces Apoptotic Cell Death in U937 Leukemia Cells through Caspase- and Mitochondria-dependent Pathways

JAI-SING YANG, CHE-WEI LIU, YI-SHIH MA, SHU-WEN WENG, NOU-YING TANG, SHIN-HWAR WU, BIN-CHUANI JI, CHIA-YU MA, YANG-CHING KO, SHINJI FUNAYAMA and CHAO-LIN KUO
In Vivo November 2012, 26 (6) 971-978;
JAI-SING YANG
1Department of Pharmacology, China Medical University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHE-WEI LIU
2Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YI-SHIH MA
3Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
4Department of Chinese Medicine, Changhua Hospital, Department of Health, Executive Yuan, Changhua, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHU-WEN WENG
3Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
5Department of Chinese Medicine, Taichung Hospital, Department of Health, Executive Yuan, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
NOU-YING TANG
6School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHIN-HWAR WU
7Division of Critical Care Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
BIN-CHUANI JI
8Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHIA-YU MA
9Department of Food and Beverage Management, Taipei Chengshih University of Science and Technology, Taipei, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YANG-CHING KO
10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHINJI FUNAYAMA
11Department of Medicinal Chemistry, Nihon Pharmaceutical University, Saitama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHAO-LIN KUO
12School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: clkuo@mail.cmu.edu.tw
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Chlorogenic acid exists widely in edible and medicinal plants and acts as an antioxidant. It is known to exert antitumor activity via induction of apoptosis in many human cancer cells. However, its signaling pathway in human leukemia cells still remains unclear. Therefore, we investigated the roles of reactive oxygen species (ROS), mitochondria and caspases during chlorogenic acid-induced apoptosis of U937 human leukemia cells. Chlorogenic acid exhibited a strong cytotoxicity and induced apoptosis in U937 cells, as determined by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Chlorogenic acid induced apoptosis by promoting ROS production and reduced the mitochondrial membrane potential (ΔΨm), as assayed by flow cytometry. Furthermore, the activity of caspase-3 was evaluated and results indicated that chlorogenic acid promoted caspase-3 activity in U937 cells. Results from western blot analysis showed that chlorogenic acid promoted expression of caspase-3, -7, -8 and -9 in U937 cells. Taken together, these results suggest that chlorogenic acid may induce apoptosis by reducing the levels of ΔΨm and by increasing the activation of caspase-3 pathways in human leukemia U937 cells in vitro.

  • Chlorogenic acid
  • apoptosis
  • U937 leukemia cells
  • caspases
  • mitochondrial dysfunction

Development of drug resistance in tumor cells and side-effects in patients have led to limitations to current chemotherapy in patients with leukemia (1, 2). In clinical practice, camptothecin from Camptotheca acuminata and paclitaxel from Taxus brevifolia, originating from natural products, are currently used as chemotherapeutic agents (3); both compounds can induce cell cytotoxic effects, including the induction of cell-cycle arrest and apoptosis (4, 5).

It is well-known that caspases (a group of cysteine proteases) play important roles in apoptosis. After injury to mitochondria, cytochrome c and other apoptotic-inducing factors can be released from mitochondria and then also activate caspase-3, -7 or -9 signals (6, 7). Thus, agents which can induce caspase activation may lead to the induction of apoptosis and it has been recognized that induction of cancercell apoptosis is the best strategy for blocking cancer development (8-10).

Chlorogenic acid, a dietary polyphenol with a long history of use in Chinese medicine, exists widely in edible and medicinal plants (11). Chlorogenic acid has been reported to have antioxidant activities (12), and is beneficial in oxidative stress-related diseases (13-16). It has also anti carcinogenic activities (16), including induction of apoptosis in human oral squamous cell carcinoma and salivary gland tumor cell lines (17), and BCR−-ABL+ chronic myeloid leukemia (CML) cells (18). However, there is no report regarding chlorogenic acid-induced apoptosis in leukemia cells. The present study investigated the cytotoxic effects of chlorogenic acid on U937 human myelocytic leukemic cells.

Materials and Methods

Chemicals and reagents. Chlorogenic acid, dimethyl sulfoxide (DMSO), propidium iodide (PI), Tris-HCl, Triton X-100 and trypan blue were purchased from Sigma-Aldrich Corp. (St. Louis, MO, USA). RPMI-1640 medium, L-glutamine, fetal bovine serum (FBS), penicillin-streptomycin, trypsin-EDTA and 4,6-diamidino-2-phenylindole dihydrochloride (DAPI), were obtained from Gibco Life Technologies (Grand Island, NY, USA). The caspase-3 substrate kit Ac-Asp-Glu-Val-Asp-chromophore p-nitroaniline (Ac-DEVD-pNA) was obtained from R&D Systems Inc. (Minneapolis, MN, USA).

Cell culture. The U937 human myelocytic leukemic cell line was from the Food Industry Research and Development Institute (Hsinchu, Taiwan, ROC). U937 cells were placed in 75-cm2 culture flasks and were grown in RPMI-1640 supplemented with 10% FBS, 100 U/ml penicillin-100 μg/ml streptomycin in a humidified atmosphere of 5% CO2 and 95% air at 37°C (19).

Determination of cell viability and morphology. U937 cells were plated at a density of 5×105 cells/well in a 12-well plate for 24 h, then were incubated with 0, 50, 100, 150 and 200 μM of chlorogenic acid at 37°C, with 5% CO2 and 95% air for 48 h. Cells were examined and photographed by phase-contrast microscopy for the examination of morphological changes. Then cells were harvested by centrifugation and were stained with PI (4 μg/ml) then analyzed by flow cytometry (FACSCalibur flow cytometer; BD Biosciences, San Jose, CA, USA) for viability measurements, as previously described (19, 20).

DAPI staining. For DAPI staining, approximately 5×104 U937 cells/ml were treated with 0, 100, 150 and 200 μM of chlorogenic acid for 48 h. Cells in each well were stained with DAPI, then examined and photographed using a fluorescence microscope as previously described (21, 22).

Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. For TUNNEL staining, approximately 5×104 cells/ml of U937 cells were treated with 0, 100, 150 and 200 μM of chlorogenic acid for 48 h. Cultured U937 cells were recovered and were attached to coverslips covered with poly-L-lysine and fixed with 4% paraformaldehyde (PFA) for 10 min at room temperature, then were washed with phosphate-buffered saline (PBS). Then the samples were mounted with Vectashield (Vector Laboratories Inc., Burlingame, CA, USA) and examined under an Olympus BH2 epifluorescense microscope (Olympus, Tokyo, Japan). The TUNEL-positive cells were quantified in random fields as a percentage of the total number of U937 cells in the field (23, 24).

Caspase-3 activity assay. Caspase-3 activity was measured through the absorbance at 405 nm after cleavage of synthetic substrate Ac-DEVD-pNA. U937 cells were plated at a density of 5×105 cells/well in T75 flasks for 24 h, and were then incubated with 0, 50, 100, 150 and 200 μM of chlorogenic acid at 37°C, with 5% CO2 and 95% air for 48 h. At the end of the incubation, cells were collected and lysed on ice for 30 min in the cell lysis buffer with the R&D system colorimetric assay kit. The lysates (50 mg) were reacted with 50 mM Ac-DEVD-pNA in a reaction buffer (1% NP-40, 20 mM Tris–HCl, 137 mM NaCl, 10% glycerol, 10 mM dithiothreitol, and protease inhibitors, pH 7.4), then the mixtures were maintained at 37°C for 2 h and subsequently analyzed in an enzyme-linked immunosorbent assay reader (Molecular Devices). The enzyme activity was calculated on the basis of a standard curve prepared using p-nitroanaline (pNA), as described previously (19, 25). The relative levels of pNA were normalized against the protein concentration under each treatment.

Detection of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm). U937 cells were placed at a density of 5×105 cells/well in a 12-well plate for 24 h, then were incubated with 0, 50, 100, 150 and 200 μM of chlorogenic acid at 37°C with 5% CO2 and 95% air for 12 h. Cells from each treatment were harvested and re-suspended in 500 μl of 10 μM (DCFH-DA; 2,7- dichlorodihydrofluorescein diacetate) for ROS and in 500 μl of 1 μM dihexyloxacarbocyanine iodide (DiOC6) for ΔΨm. Cells were incubated at 37°C for 30 min before being analyzed by flow cytometry, as described previously (21, 22).

Western blotting of apoptosis-associated proteins. Approximately 1×107 cells of U937 cells in 6-well plates were then treated with 0, 50, 100, 150 and 200 μM of chlorogenic acid for 48 h. Cells were harvested and lysed with lysis buffer (PRO-PREP™ protein extraction solution, iNtRON Biotechnology, Seongnam-si, Gyeonggi-do, Korea). The total proteins from each treatment were quantified and 30 μg were used for western blot analysis and all samples were analyzed using 10% Tris-glycine-SDS-polyacrylamide gels for 30 min and then the proteins were transferred to a nitrocellulose membrane by electroblotting, as described previously (19-22). The membranes were stained with primary antibodies against caspase-3, -8, -9 and -7 (R&D Systems) then were washed and incubated with a secondary antibody for enhanced chemiluminescence (Immobilon Western HRP substrate, Merck Millipore, Bedford, MA, USA), as described previously (21, 26).

Results

Chlorogenic acid reduces cell viability and induces morphological changes of U937 cells. After exposure to 0, 50, 100, 150 or 200 μM of chlorogenic acid for 48 h, cells were examined and photographed under phase-contrast microscopy and the results are shown in Figure 1A. The results indicated that cell death in chlorogenic acid-treated cells was greater, based on the higher level of cell debris compared to those of control, leading to lower cell numbers. These effects were concentration-dependent. The cytotoxic effects of chlorogenic acid on U937 cells were examined by flow cytometric assay and the results are shown in Figure 1B. The results indicated that chlorogenic acid treatment caused a concentration-dependent decrease in the viability of U937 cells.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Chlorogenic acid reduced cell viability and induced cell morphological changes of U937 cells. Cells were incubated with different concentrations of chlorogenic acid for 24 and 48 h. The viability of cells measured (A) and cell morphological changes were examined as described in the Materials and Methods. Each point corresponds to the mean±SD (n=3), ***p<0.001 for the difference between chlorogenic acid, cells treated and control in U937 cell.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Chlorogenic acid induced apoptosis in U937 cells. Cells at a density of 1×105 cells/well were incubated with different concentrations of chlorogenic acid for 48 h. Cells were stained with 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) for 30 min, then were examined and photographed under a fluorescence microscope, as described in Materials and Methods.

Chlorogenic acid induces apoptosis of U937 cells. For further investigating the mode of death of U937 cells after exposure to chlorogenic acid, cells were exposed to chlorogenic acid (0, 100, 150 or 200 μM) for 48 h and were then staining by DAPI for examination of apoptotic cell death. The results are shown in Figure 2, and indicate that chlorogenic acid induced apoptosis based on the higher number of white-colored nuclei in treated cells compared to those of the control.

Chlorogenic acid induces DNA fragmentation (apoptosis) in U937 cells. Cells were exposed to different concentrations (0, 50, 100, 150 or 200 μM) of chlorogenic acid for 24 h, then were stained with TUNEL and photographed and the results are shown in Figure 3. In the TUNEL assay, chlorogenic acid treatment increased the number of cells with DNA strand breaks in a dose-related manner (Figure 3). Chlorogenic acid induces caspase-3 activation of U937 cells. Cells were exposed to different concentration of chlorogenic acid for 24 h, then were lysed for measuring the activitiy of caspase-3 by using enzyme-linked immunosorbent assay and the results are shown in Figure 4.

Chlorogenic acid induces ROS production and affects the level of ΔΨm in U937 cells. To confirm whether chlorogenic acid induces apoptosis via the mitochondrial pathway, U937 cells were treated with 0, 100, 150 and 200 μM chlorogenic acid for 12 h, and the ROS levels and ΔΨm were measured and determined by flow cytometric assay. As shown in Figure 5A and B, chlorogenic acid treatment of U937 cells led to an increase in the production of ROS (Figure 5A) and also induced a decrease of ΔΨm (Figure 5B). These effects were concentration-dependent.

Chlorogenic acid affects the levels of apoptosis proteins in U937 cells. To investigate whether chlorogenic acid induced apoptosis-involved caspase-associated protein expression, U937 cells were exposed to chlorogenic acid and then cells were harvested for western blotting. As shown in Figure 6, chlorogenic acid promoted the expression of caspase-3, -7, -8 and -9 proteins, which suggests that chlorogenic acid induced apoptosis in U937 cells through a caspase-dependent pathway.

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Chlorogenic acid induced DNA fragmentation (apoptosis) in U937 cells. Cells at a density of 1×105 cells/well were incubated with different concentrations of chlorogenic acid for 48 h. Then cells were stained by the TUNEL assay for 30 min then were examined and photographed under a fluorescence microscope, as described in the Materials and Methods. ***p<0.001.

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

Chlorogenic acid induced caspase-3 activation in U937 cells. Cells at a density of 1×105 cells/well were incubated with different concentrations of chlorogenic acid for 48 h. The cells were lysed and incubated with caspase-3 substrate (Ac-DEVD-pNA) and the activity of caspase-3 was measured by enzyme-linked immunosorbent assay, as described in the Materials and Methods. ***p<0.001 for the difference between chlorogenic acid-treated and control U937 cells.

Figure 5.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 5.

Chlorogenic acid induced reactive oxygen species (ROS) production and affected the level of mitochondrial membrane potential (ΔΨm) in U937 cells. Cells (2×105 cells/ml) were treated with chlorogenic acid for 12 h. Cells were harvested for analysis of ROS (A) and ΔΨm (B), as shown by staining by 2,7- dichlorodihydrofluorescein diacetate (DCFH-DA) and dihexyloxacarbocyanine iodide (DiOC6), respectively. The stained cells were determined by flow cytometry, as described in the Materials and Methods. Values are means±SD (n=3). *Significantly different from that at 0 h treatment (control group) at ***p<0.001.

Discussion

Natural products such as camptothecin and paclitaxel have been developed as anticancer agents in the clinical setting (27, 28). Chlorogenic acid exists in natural plants and although studies have shown that chlorogenic acid induces cytotoxic effects in many human cancer cells (13-16), the underlying signal transduction pathway in human leukemia cells is still unclear. Therefore, the present study focused on the elucidation of the role of caspases and mitochondria during apoptosis of U937 human leukemia cells, induced by chlorogenic acid. We found that chlorogenic acid had a strong cytotoxicity towards U937 cells in a dose-dependent manner (Figure 1). However, the effective concentration for cytotoxicity of chlorogenic acid towards U937 cells was found to be greater than 100 μM (Figure 1). Furthermore, we also found that caspase-3, -7, -8 and -9 were activated prior to the development of apoptosis in U937 cells exposed to chlorogenic acid (Figure 6).

Figure 6.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 6.

Chlorogenic acid affects the level of apoptosis-related proteins in U937 cells. Cells were treated with chlorogenic acid for 48 h then the total proteins were prepared and detected by western blotting as described in the Materials and Methods. Primary antibodies for caspase-3, -7, -8 and -9 were used for western blotting. Ctl: control untreated cells.

Results from Figure 1A and B demonstrate that chlorogenic acid induced cytotoxicity (i.e. reduced the percentage of viable cells). In order to confirm whether chlorogenic acid induces cell death through the induction of apoptosis of U937 cells or not, we used DAPI staining for examining the apoptosis and TUNEL assays to show the presence of DNA fragmentation. Results from DAPI and TUNEL assay also showed that chlorogenic acid induced apoptosis (DNA fragmentation) in U937 cells.

It is well-documented that apoptosis can be divided into caspase-dependent and -independent and mitochondria-dependent and -independent signal pathways (6, 7). Our results showed that chlorogenic acid induced apoptosis through the activation of caspase-3 which was measured by using substrate of caspase-3. We also used the caspase-3 inhibitor, z-VAD-FMK, which significantly reduced the caspase-3 activation and increased the percentage of viable cells upon treatment with chlorogenic acid (data not shown).

It has also been reported that agents which induce apoptosis can be divided into mitochondria-dependent and - independent pathways (7). If an agent induced apoptosis through Fas-FasL then activated caspase-8, followed by caspase-3 then led to apoptosis, then this is called mitochondria-independent (caspase-dependent) pathway. If an agent led to cytochrome c release and promoted caspase-9 activation then led to apoptosis or AIF and Endo-G release, to cause apoptosis, then this is called mitochondria-dependent pathway (29, 30). Here, we also used flow cytometry to assay the levels of mitochondia membrane potential and results indicated that chlorogenic acid decreases the levels of ΔΨm in U937 cells (Figure 4B). This indicated that chlorogenic acid induced apoptosis in U937 cells through a mitochondria-dependent pathway.

It is well-known that ROS play an important physiological role, such as they can act as secondary messengers to promote or suppress the expression of a number of genes and/or signal transduction pathways (31, 32). It was reported that maintenance of the homeostasis of ROS is critical in cell signaling and in the regulation of cell death (31). It was also reported that tumor cells have higher levels of ROS than their normal counterparts; tumor cells are more sensitive to the additional oxidative stress generated by anticancer agents (33). Here, we also used flow cytometric assays for measuring the ROS production in U937 cells, after exposure to chlorogenic acid, and the results indicated that chlorogenic acid promoted ROS production in U937 cells (Figure 4). This is in agreement with another report demonstrating that chlorogenic acid induced apoptosis via ROS production in cancer cells (18). Thus, we also suggest that chlorogenic acid induced apoptosis of U937 cells through the ROS production.

Figure 7.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 7.

Proposed model for chlorogenic acid-triggered apoptosis of human leukemia U937 cells. BCL-2, B-cell lymphoma 2; Cyto c, cytochrome c; PARP, Poly (ADP-ribose) polymerase; AIF, apoptosis-inducing factor; Endo G, Endonuclease G.

In conclusion, our study suggests that chlorogenic acid-induced cytotoxic effects occur through induction of apoptosis by the disruption of the mitochondrial membrane potential (reduction of ΔΨm), ROS production, activation of caspase-3, -7, -8 and -9 induction of apoptosis, as summarized in Figure 7.

Acknowledgements

This work was supported by the National Science Council, Republic of China (Taiwan) (NSC 100-2815-C-039-056-B).

Footnotes

  • Conflicts of Interest

    None of the Authors have any conflict of interest to declare.

  • Received May 22, 2012.
  • Revision received September 18, 2012.
  • Accepted September 19, 2012.
  • Copyright © 2012 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved

References

  1. ↵
    1. Sitaresmi MN,
    2. Mostert S,
    3. Purwanto I,
    4. Gundy CM,
    5. Sutaryo,
    6. Veerman AJ
    : Chemotherapy-related side effects in childhood acute lymphoblastic leukemia in indonesia: parental perceptions. J Pediatr Oncol Nurs 26(4): 198-207, 2009.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Itzykson R,
    2. Ayari S,
    3. Vassilief D,
    4. Berger E,
    5. Slama B,
    6. Vey N,
    7. Suarez F,
    8. Beyne-Rauzy O,
    9. Guerci A,
    10. Cheze S,
    11. Thomas X,
    12. Stamatoullas A,
    13. Gardembas M,
    14. Bauduer F,
    15. Kolb A,
    16. Chaury MC,
    17. Legros L,
    18. Damaj G,
    19. Chermat F,
    20. Dreyfus F,
    21. Fenaux P,
    22. Ades L
    : Is there a role for all-trans retinoic acid in combination with recombinant erythropoetin in myelodysplastic syndromes? A report on 59 cases. Leukemia 23(4): 673-678, 2009.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Wall ME,
    2. Wani MC
    : Camptothecin and taxol: discovery to clinic – thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res 55(4): 753-760, 1995.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Debernardis D,
    2. Cimoli G,
    3. Parodi S,
    4. Russo P
    : Interactions between taxol and camptothecin. Anticancer Drugs 7(5): 531-534, 1996.
    OpenUrlPubMed
  5. ↵
    1. Tonini T,
    2. Gabellini C,
    3. Bagella L,
    4. D'Andrilli G,
    5. Masciullo V,
    6. Romano G,
    7. Scambia G,
    8. Zupi G,
    9. Giordano A
    : pRb2/p130 decreases sensitivity to apoptosis induced by camptothecin and doxorubicin but not by taxol. Clin Cancer Res 10(23): 8085-8093, 2004.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Kluck RM,
    2. Bossy-Wetzel E,
    3. Green DR,
    4. Newmeyer DD
    : The release of cytochrome c from mitochondria: A primary site for Bcl-2 regulation of apoptosis. Science 275(5303): 1132-1136, 1997.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Lavrik IN,
    2. Golks A,
    3. Krammer PH
    : Caspases: pharmacological manipulation of cell death. J Clin Invest 115(10): 2665-2672, 2005.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Liu W,
    2. Lee HW,
    3. Liu Y,
    4. Wang R,
    5. Rodgers GP
    : Olfactomedin 4 is a novel target gene of retinoic acids and 5-aza-2’-deoxycytidine involved in human myeloid leukemia cell growth, differentiation, and apoptosis. Blood 116(23): 4938-4947, 2010.
    OpenUrlAbstract/FREE Full Text
    1. Sakoe Y,
    2. Sakoe K,
    3. Kirito K,
    4. Ozawa K,
    5. Komatsu N
    : FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia. Blood 115(18): 3787-3795, 2010.
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Lu CC,
    2. Yang JS,
    3. Chiang JH,
    4. Hour MJ,
    5. Lin KL,
    6. Lin JJ,
    7. Huang WW,
    8. Tsuzuki M,
    9. Lee TH,
    10. Chung JG
    : Novel quinazolinone MJ-29 triggers endoplasmic reticulum stress and intrinsic apoptosis in murine leukemia WEHI-3 cells and inhibits leukemic mice. PLoS ONE 7(5): e36831, 2012.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Bouayed J,
    2. Rammal H,
    3. Dicko A,
    4. Younos C,
    5. Soulimani R
    : Chlorogenic acid, a polyphenol from Prunus domestica (Mirabelle), with coupled anxiolytic and antioxidant effects. J Neurol Sci 262(1-2): 77-84, 2007.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Kono Y,
    2. Kashine S,
    3. Yoneyama T,
    4. Sakamoto Y,
    5. Matsui Y,
    6. Shibata H
    : Iron chelation by chlorogenic acid as a natural antioxidant. Biosci Biotechnol Biochem 62(1): 22-27, 1998.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Rodriguez de Sotillo DV,
    2. Hadley M
    : Chlorogenic acid modifies plasma and liver concentrations of: cholesterol, triacylglycerol, and minerals in (fa/fa) Zucker rats. J Nutr Biochem 13(12): 717-726, 2002.
    OpenUrlCrossRefPubMed
    1. Jin UH,
    2. Lee JY,
    3. Kang SK,
    4. Kim JK,
    5. Park WH,
    6. Kim JG,
    7. Moon SK,
    8. Kim CH
    : A phenolic compound, 5-caffeoylquinic acid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9 inhibitor: isolation and identification from methanol extract of Euonymus alatus. Life Sci 77(22): 2760-2769, 2005.
    OpenUrlCrossRefPubMed
    1. Suzuki A,
    2. Fujii A,
    3. Yamamoto N,
    4. Yamamoto M,
    5. Ohminami H,
    6. Kameyama A,
    7. Shibuya Y,
    8. Nishizawa Y,
    9. Tokimitsu I,
    10. Saito I
    : Improvement of hypertension and vascular dysfunction by hydroxyhydroquinone-free coffee in a genetic model of hypertension. FEBS Lett 580(9): 2317-2322, 2006.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Tanaka T,
    2. Nishikawa A,
    3. Shima H,
    4. Sugie S,
    5. Shinoda T,
    6. Yoshimi N,
    7. Iwata H,
    8. Mori H
    : Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters. Basic Life Sci 52: 429-440, 1990.
    OpenUrlPubMed
  14. ↵
    1. Jiang Y,
    2. Kusama K,
    3. Satoh K,
    4. Takayama E,
    5. Watanabe S,
    6. Sakagami H
    : Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines. Phytomedicine 7(6): 483-491, 2000.
    OpenUrlPubMed
  15. ↵
    1. Rakshit S,
    2. Mandal L,
    3. Pal BC,
    4. Bagchi J,
    5. Biswas N,
    6. Chaudhuri J,
    7. Chowdhury AA,
    8. Manna A,
    9. Chaudhuri U,
    10. Konar A,
    11. Mukherjee T,
    12. Jaisankar P,
    13. Bandyopadhyay S
    : Involvement of ROS in chlorogenic acid-induced apoptosis of Bcr-Abl+ CML cells. Biochem Pharmacol 80(11): 1662-1675, 2010.
    OpenUrlPubMed
  16. ↵
    1. Yang JS,
    2. Hour MJ,
    3. Huang WW,
    4. Lin KL,
    5. Kuo SC,
    6. Chung JG
    : MJ-29 inhibits tubulin polymerization, induces mitotic arrest, and triggers apoptosis via cyclin-dependent kinase 1-mediated Bcl-2 phosphorylation in human leukemia U937 cells. J Pharmacol Exp Ther 334(2): 477-488, 2010.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Lu CC,
    2. Yang JS,
    3. Huang AC,
    4. Hsia TC,
    5. Chou ST,
    6. Kuo CL,
    7. Lu HF,
    8. Lee TH,
    9. Wood WG,
    10. Chung JG
    : Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res 54(7): 967-976, 2010.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Chiang JH,
    2. Yang JS,
    3. Ma CY,
    4. Yang MD,
    5. Huang HY,
    6. Hsia TC,
    7. Kuo HM,
    8. Wu PP,
    9. Lee TH,
    10. Chung JG
    : Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways. Chem Res Toxicol 24(1): 20-29, 2011.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Yu FS,
    2. Yang JS,
    3. Yu CS,
    4. Lu CC,
    5. Chiang JH,
    6. Lin CW,
    7. Chung JG
    : Safrole induces apoptosis in human oral cancer HSC-3 cells. J Dent Res 90(2): 168-174, 2011.
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Wu PP,
    2. Liu KC,
    3. Huang WW,
    4. Ma CY,
    5. Lin H,
    6. Yang JS,
    7. Chung JG
    : Triptolide induces apoptosis in human adrenal cancer NCI-H295 cells through a mitochondrial-dependent pathway. Oncol Rep 25(2): 551-557, 2011.
    OpenUrlPubMed
  21. ↵
    1. Chung JG,
    2. Yang JS,
    3. Huang LJ,
    4. Lee FY,
    5. Teng CM,
    6. Tsai SC,
    7. Lin KL,
    8. Wang SF,
    9. Kuo SC
    : Proteomic approach to studying the cytotoxicity of YC-1 on U937 leukemia cells and antileukemia activity in orthotopic model of leukemia mice. Proteomics 7(18): 3305-3317, 2007.
    OpenUrlCrossRefPubMed
  22. ↵
    1. Huang WW,
    2. Chiu YJ,
    3. Fan MJ,
    4. Lu HF,
    5. Yeh HF,
    6. Li KH,
    7. Chen PY,
    8. Chung JG,
    9. Yang JS
    : Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells. Mol Nutr Food Res 54(11): 1585-1595, 2010.
    OpenUrlCrossRefPubMed
  23. ↵
    1. Ji BC,
    2. Hsu WH,
    3. Yang JS,
    4. Hsia TC,
    5. Lu CC,
    6. Chiang JH,
    7. Yang JL,
    8. Lin CH,
    9. Lin JJ,
    10. Suen LJ,
    11. Gibson Wood W,
    12. Chung JG
    : Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem 57(16): 7596-7604, 2009.
    OpenUrlCrossRefPubMed
  24. ↵
    1. Newman DJ,
    2. Cragg GM,
    3. Holbeck S,
    4. Sausville EA
    : Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy. Curr Cancer Drug Targets 2(4): 279-308, 2002.
    OpenUrlCrossRefPubMed
  25. ↵
    1. Oberlies NH,
    2. Kroll DJ
    : Camptothecin and taxol: historic achievements in natural products research. J Nat Prod 67(2): 129-135, 2004.
    OpenUrlCrossRefPubMed
  26. ↵
    1. Kadowaki H,
    2. Nishitoh H,
    3. Ichijo H
    : Survival and apoptosis signals in ER stress: the role of protein kinases. J Chem Neuroanat 28(1-2): 93-100, 2004.
    OpenUrlPubMed
  27. ↵
    1. Oyadomari S,
    2. Mori M
    : Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11(4): 381-389, 2004.
    OpenUrlCrossRefPubMed
  28. ↵
    1. Green DR,
    2. Reed JC
    : Mitochondria and apoptosis. Science 281(5381): 1309-1312, 1998.
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. Orrenius S
    : Reactive oxygen species in mitochondria-mediated cell death. Drug Metab Rev 39(2-3): 443-455, 2007.
    OpenUrlCrossRefPubMed
  30. ↵
    1. Kuo YF,
    2. Su YZ,
    3. Tseng YH,
    4. Wang SY,
    5. Wang HM,
    6. Chueh PJ
    : Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. Free Radic Biol Med 49(2): 214-226, 2010.
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

In Vivo: 26 (6)
In Vivo
Vol. 26, Issue 6
November-December 2012
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on In Vivo.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Chlorogenic Acid Induces Apoptotic Cell Death in U937 Leukemia Cells through Caspase- and Mitochondria-dependent Pathways
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
5 + 2 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Chlorogenic Acid Induces Apoptotic Cell Death in U937 Leukemia Cells through Caspase- and Mitochondria-dependent Pathways
JAI-SING YANG, CHE-WEI LIU, YI-SHIH MA, SHU-WEN WENG, NOU-YING TANG, SHIN-HWAR WU, BIN-CHUANI JI, CHIA-YU MA, YANG-CHING KO, SHINJI FUNAYAMA, CHAO-LIN KUO
In Vivo Nov 2012, 26 (6) 971-978;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Chlorogenic Acid Induces Apoptotic Cell Death in U937 Leukemia Cells through Caspase- and Mitochondria-dependent Pathways
JAI-SING YANG, CHE-WEI LIU, YI-SHIH MA, SHU-WEN WENG, NOU-YING TANG, SHIN-HWAR WU, BIN-CHUANI JI, CHIA-YU MA, YANG-CHING KO, SHINJI FUNAYAMA, CHAO-LIN KUO
In Vivo Nov 2012, 26 (6) 971-978;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites
  • Effects of Coffee Intake on Oxidative Stress During Aging-related Alterations in Periodontal Tissue
  • Google Scholar

More in this TOC Section

  • Systemic Administration of Lipopolysaccharide from Porphyromonas gingivalis Decreases Neprilysin Expression in the Mouse Hippocampus
  • Monitoring T-Cell Kinetics in the Early Recovery Period of Lung Transplantation Cases by Copy Number Levels of T-Cell Receptor Excision Circle
  • Successful Surgical Outcome of Feline Inductive Odontogenic Tumor in Three Cats
Show more Experimental Studies

Similar Articles

Keywords

  • Chlorogenic acid
  • apoptosis
  • U937 leukemia cells
  • caspases
  • mitochondrial dysfunction
In Vivo

© 2023 In Vivo

Powered by HighWire