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

Anticancer Drugs. 2013 Jun;24(5):455-60.

Hee-Seok Leea, Chanvorleak Phata, Sang-Un Choib, Chan Leea*

aDepartment of Food Science and Technology, Chung-Ang University, Anseong, 456-756, Republic of Korea

bKorea Research Institute of Chemical Technology, Daejeon, 305-600, Republic of Korea

 

Abstract

NeoN-methylsansalvamide is a novel low-molecular-weight cyclic pentadepsipeptide, exhibiting cytotoxic effects on various human cancer cell lines. Its structural analysis by liquid chromatography mass/mass spectrometry revealed the cyclic structure sequence −phenylalanine−luecine−valine−N-methylluecine−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 sulforhodamine B assay. The EC50 values of paclitaxel for MES-SA, HCT15, and the multidrug resistance sublines MES-SA/DX5 and HCT15/CL05 were 1.00 ± 0.20, 0.85 ± 0.63, 10.00 ± 0.53, and >1,000 nM, respectively. However, the EC50 values of pacliraxel including 3 μM neoN-methylsansalvamide for MES-SA/DX5, HCT15, and HCT15/CL02 were 1.58 ± 0.12, 0.10 ± 0.02, and 288.40 ± 21.02 nM, 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 at reversing multidrug resistance in vitro, and this activity may be a major applicable biological function of this compound.

PMID: 23411682

 

Supplementary

Chan Lee-png1

Chan Lee-png2

The full-scan positive ion ESI-MS spectrum of neoN-methylsansalvamide produced by F. solani KCCM90040 showed the protonated molecular ion at m/z 601.59. Further information on the fragmentation in ESI-MS/MS analysis revealed clear serial loss of the subunits through cleavage across the ester and amide bonds from the ion at 573.59 which was produced by the loss of −CO after opening of the cyclic molecule. In general, cyclic depsipeptides afforded [M+H−28]+ ions in MS/MS data due to the loss of –CO after opening of the cyclic molecule to carbonyl carbon. The next fragment ions in the spectra were created by the sequential loss of Phe, Leu and Val at m/z 454.51 (M+H−Phe), 340.92 (M+H−Phe−Leu) and 214.25 (M+H−Phe−Leu−Val−CO), respectively.

 

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