PT  - JOURNAL ARTICLE
AU  - CLAUDIO PLAZA
AU  - MARIO PAVANI
AU  - RAMIRO ARAYA-MATURANA
AU  - JAQUELINE PEZOA
AU  - JUAN DIEGO MAYA
AU  - ANTONIO MORELLO
AU  - MARIA INÉS BECKER
AU  - ALFREDO DE IOANNES
AU  - JORGE FERREIRA
TI  - Chemosensitizing Effect of Nordihydroguaiaretic Acid and its Tetra-acetylated Derivative on Parental and Multiresistant TA3 Mouse Mammary Adenocarcinoma Cells
DP  - 2009 Nov 01
TA  - In Vivo
PG  - 959--967
VI  - 23
IP  - 6
4099  - http://iv.iiarjournals.org/content/23/6/959.short
4100  - http://iv.iiarjournals.org/content/23/6/959.full
SO  - In Vivo2009 Nov 01; 23
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.