Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya Majuscula

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2012 Jul 24

PMID 22822361

Citations 16

Authors

Ashootosh Tripathi

Wanru Fang

David Tai Leong

Lik Tong Tan

Affiliations

Soon will be listed here.

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.

Citing Articles

From Beach to the Bedside: Harnessing Mitochondrial Function in Human Diseases Using New Marine-Derived Strategies.

Mirra S, Marfany G Int J Mol Sci. 2024; 25(2).

PMID: 38255908 PMC: 10815353. DOI: 10.3390/ijms25020834.

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents.

Ribeiro R, Costa L, Pinto E, Sousa E, Fernandes C Mar Drugs. 2023; 21(12).

PMID: 38132930 PMC: 10745025. DOI: 10.3390/md21120609.

Total Syntheses of Colletopeptide A and Colletotrichamide A.

Chen J, Jiang Y, Yan J, Xu C, Ye T Molecules. 2023; 28(20).

PMID: 37894673 PMC: 10608858. DOI: 10.3390/molecules28207194.

Targeted and functional genomics approaches to the mechanism of action of lagunamide D, a mitochondrial cytotoxin from marine cyanobacteria.

Luo D, Ratnayake R, Atanasova K, Paul V, Luesch H Biochem Pharmacol. 2023; 213:115608.

PMID: 37201874 PMC: 10353561. DOI: 10.1016/j.bcp.2023.115608.

Marine Cyanobacteria as Sources of Lead Anticancer Compounds: A Review of Families of Metabolites with Cytotoxic, Antiproliferative, and Antineoplastic Effects.

Robles-Banuelos B, Duran-Riveroll L, Rangel-Lopez E, Perez-Lopez H, Gonzalez-Maya L Molecules. 2022; 27(15).

PMID: 35956762 PMC: 9369884. DOI: 10.3390/molecules27154814.

References

Chen Q, Liu Y, Luesch H . Systematic Chemical Mutagenesis Identifies a Potent Novel Apratoxin A/E Hybrid with Improved in Vivo Antitumor Activity. ACS Med Chem Lett. 2011; 2(11):861-865. PMC: 3212850. DOI: 10.1021/ml200176m. View

Lowe S, Cepero E, Evan G . Intrinsic tumour suppression. Nature. 2004; 432(7015):307-15. DOI: 10.1038/nature03098. View

Fulda S, Debatin K . Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006; 25(34):4798-811. DOI: 10.1038/sj.onc.1209608. View

Tripathi A, Puddick J, Prinsep M, Rottmann M, Tan L . Lagunamides A and B: cytotoxic and antimalarial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. J Nat Prod. 2010; 73(11):1810-4. DOI: 10.1021/np100442x. View

Nakao Y, Yoshida W, Takada Y, Kimura J, Yang L, Mooberry S . Kulokekahilide-2, a cytotoxic depsipeptide from a cephalaspidean mollusk Philinopsis speciosa. J Nat Prod. 2004; 67(8):1332-40. DOI: 10.1021/np049949f. View

Ng K, Khoo S, Heng B, Setyawati M, Tan E, Zhao X . The role of the tumor suppressor p53 pathway in the cellular DNA damage response to zinc oxide nanoparticles. Biomaterials. 2011; 32(32):8218-25. DOI: 10.1016/j.biomaterials.2011.07.036. View

Spierings D, Mcstay G, Saleh M, Bender C, Chipuk J, Maurer U . Connected to death: the (unexpurgated) mitochondrial pathway of apoptosis. Science. 2005; 310(5745):66-7. DOI: 10.1126/science.1117105. View

Tripathi A, Puddick J, Prinsep M, Lee P, Tan L . Hantupeptins B and C, cytotoxic cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. Phytochemistry. 2009; 71(2-3):307-11. DOI: 10.1016/j.phytochem.2009.10.006. View

Wasilewski M, Scorrano L . The changing shape of mitochondrial apoptosis. Trends Endocrinol Metab. 2009; 20(6):287-94. DOI: 10.1016/j.tem.2009.03.007. View

10.

Mishra S, Murphy L, Nyomba B, Murphy L . Prohibitin: a potential target for new therapeutics. Trends Mol Med. 2005; 11(4):192-7. DOI: 10.1016/j.molmed.2005.02.004. View

11.

Cane D, WALSH C, Khosla C . Harnessing the biosynthetic code: combinations, permutations, and mutations. Science. 1998; 282(5386):63-8. DOI: 10.1126/science.282.5386.63. View

12.

ODonnell D, Milligan L, Stark J . Induction of CD95 (Fas) and apoptosis in respiratory epithelial cell cultures following respiratory syncytial virus infection. Virology. 1999; 257(1):198-207. DOI: 10.1006/viro.1999.9650. View

13.

Sato S, Murata A, Orihara T, Shirakawa T, Suenaga K, Kigoshi H . Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin. Chem Biol. 2011; 18(1):131-9. DOI: 10.1016/j.chembiol.2010.10.017. View

14.

Tripathi A, Puddick J, Prinsep M, Lee P, Tan L . Hantupeptin A, a cytotoxic cyclic depsipeptide from a Singapore collection of Lyngbya majuscula. J Nat Prod. 2008; 72(1):29-32. DOI: 10.1021/np800448t. View

15.

Suenaga K, Kajiwara S, Kuribayashi S, Handa T, Kigoshi H . Synthesis and cytotoxicity of aurilide analogs. Bioorg Med Chem Lett. 2008; 18(14):3902-5. DOI: 10.1016/j.bmcl.2008.06.035. View

16.

Finlay C, Hinds P, Levine A . The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989; 57(7):1083-93. DOI: 10.1016/0092-8674(89)90045-7. View

17.

Tan L, Chang Y, Ashootosh T . Besarhanamides A and B from the marine cyanobacterium Lyngbya majuscula. Phytochemistry. 2008; 69(10):2067-9. DOI: 10.1016/j.phytochem.2008.04.021. View

18.

Minich S . Brentuximab vedotin: a new age in the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma. Ann Pharmacother. 2012; 46(3):377-83. DOI: 10.1345/aph.1Q680. View

19.

Hanahan D, Weinberg R . The hallmarks of cancer. Cell. 2000; 100(1):57-70. DOI: 10.1016/s0092-8674(00)81683-9. View

20.

Wrasidlo W, Mielgo A, Torres V, Barbero S, Stoletov K, Suyama T . The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8. Proc Natl Acad Sci U S A. 2008; 105(7):2313-8. PMC: 2268133. DOI: 10.1073/pnas.0712198105. View