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Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula
Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, 637616, Singapore
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive, 117576, Singapore
* Authors to whom correspondence should be addressed.
Received: 17 April 2012; in revised form: 9 May 2012 / Accepted: 10 May 2012 / Published: 23 May 2012
Abstract: Lagunamides A (1) and B (2) are potent cytotoxic cyclic depsipeptides isolated from the filamentous marine cyanobacterium, Lyngbya majuscula, from Pulau Hantu, Singapore. These compounds are structurally related to the aurilide-class of molecules, which have been reported to possess exquisite antiproliferative activities against cancer cells. The present study presents preliminary findings on the selectivity of lagunamides against various cancer cell lines as well as their mechanism of action by studying their effects on programmed cell death or apoptosis. Lagunamide A exhibited a selective growth inhibitory activity against a panel of cancer cell lines, including P388, A549, PC3, HCT8, and SK-OV3 cells, with IC50 values ranging from 1.6 nM to 6.4 nM. Morphological studies showed blebbing at the surface of cancer cells as well as cell shrinkage accompanied by loss of contact with the substratum and neighboring cells. Biochemical studies using HCT8 and MCF7 cancer cells suggested that the cytotoxic effect of 1 and 2 might act via induction of mitochondrial mediated apoptosis. Data presented in this study warrants further investigation on the mode of action and underscores the importance of the lagunamides as potential anticancer agents.
Keywords: marine cyanobacterium; cyclic depsipeptides; lagunamides; apoptosis; cytotoxicity
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MDPI and ACS Style
Tripathi, A.; Fang, W.; Leong, D.T.; Tan, L.T. Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula. Mar. Drugs 2012, 10, 1126-1137.
Tripathi A, Fang W, Leong DT, Tan LT. Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula. Marine Drugs. 2012; 10(5):1126-1137.
Tripathi, Ashootosh; Fang, Wanru; Leong, David Tai; Tan, Lik Tong. 2012. "Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula." Mar. Drugs 10, no. 5: 1126-1137.