RT Journal Article
SR Electronic
T1 Chemosensitizing Effect of Nordihydroguaiaretic Acid and its Tetra-acetylated Derivative on Parental and Multiresistant TA3 Mouse Mammary Adenocarcinoma Cells
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 959
OP 967
VO 23
IS 6
A1 PLAZA, CLAUDIO
A1 PAVANI, MARIO
A1 ARAYA-MATURANA, RAMIRO
A1 PEZOA, JAQUELINE
A1 MAYA, JUAN DIEGO
A1 MORELLO, ANTONIO
A1 BECKER, MARIA INÉS
A1 DE IOANNES, ALFREDO
A1 FERREIRA, JORGE
YR 2009
UL http://iv.iiarjournals.org/content/23/6/959.abstract
AB Background: Multidrug resistance (MDR) continues being the major obstacle for successful anticancer chemotherapy. Materials and Methods: The action of nordihydroguaiaretic acid (NDGA) and its tetra-acetylated derivative (NDGATA) on TA3 mouse mammary adenocarcinoma cells and their ability to restore doxorubicin (DOX), cisplatin (CPT) and methotrexate (MTX) sensitivity of the multiresistant variant TA3-MTX-R was examined. Results: Both NDGA and NDGATA synergistically enhanced the cytotoxicity of DOX, CPT and MTX, with a more evident effect in the TA3-MTX-R than in the TA3 cells. NDGATA was more effective than NDGA, as analyzed by the isobologram method. The combination of NDGATA and DOX also reduced the tumor growth rate in mice. Although it did not prolong the median survival time, 30% of mice showed no vestiges of tumor 200 days after implantation with either TA3 or TA3-MTX-R cells. Moreover, NDGA and NDGATA increased the accumulation of DOX and rhodamine (RHO) 123 in both cell lines. Conclusion: NDGA and NDGATA are able to chemosensitize tumor cells and combination therapy with NDGATA and DOX is effective at inhibiting tumor growth in mice.