title: 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 -phenylalanine-leucine-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 μmol/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.
authors: Department of Food Science and Technology, Chung-Ang University, Anseong.
authors: Hee-Seok
authors: HS
authors: Lee
authors: Chanvorleak
authors: C
authors: Phat
authors: Sang-Un
authors: SU
authors: Choi
authors: Chan
authors: C
authors: Lee
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry
chemical_list: D047630:Depsipeptides; C419331:N-Methylsansalvamide; D010456:Peptides, Cyclic; C583385:neoN-methylsansalvamide; D017239:Paclitaxel