Synergistic effect of a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, and paclitaxel on human multidrug resistance cancer cell lines

Abstract

NeoN-methylsansalvamide is a novel low-molecular- weight cyclic pentadepsipeptide that exerts cytotoxic effects on various human cancer cell lines. Its structural analysis using liquid chromatography mass/mass spectrometry showed the cyclic structure sequence -phenylalanineleucine- valine-N-methylleucine-leucic acid-. The intrinsic cytotoxic and multidrug resistance reversal effects of neoN-methylsansalvamide were evaluated on the human cancer cell lines MES-SA and HCT15 as well as on their multidrug resistance sublines (MES-SA/DX5 and HCT15/CL05, respectively) using the sulforhodamine B assay. The EC50 values of paclitaxel for MES-SA, HCT15, and for the multidrug resistance sublines MES-SA/DX5 and HCT15/CL05 were 1.00 +/- 0.20, 0.85 +/- 0.63, 10.00 +/- 0.53, and > 1000 nmol/l, respectively. However, the EC50 values for paclitaxel including 3 lmol/l neoN-methylsansalvamide for MES-SA/DX5, HCT15, and HCT15/CL02 were 1.58 +/- 0.12, 0.10 +/- 0.02, and 288.40 +/- 21.02 nmol/l, respectively. The in-vitro multidrug resistance reversal activity of neoN-methylsansalvamide was similar to that of the control verapamil. These finding suggests that a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, is effective in reversing multidrug resistance in vitro, and this activity may be a major applicable biological function of this compound. Anti-Cancer Drugs 24:455-460 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Anti-Cancer Drugs 2013, 24:455-460