Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Streptochlorin Isolated from Streptomyces sp. Induces Apoptosis in Human Hepatocarcinoma Cells Through a Reactive Oxygen Species-Mediated Mitochondrial Pathway

  • Shin, Dong-Yeok (Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School) ;
  • Shin, Hee-Jae (Marine Natural Product Chemistry Laboratory, Ocean Research and Development Institute) ;
  • Kim, Gi-Young (Faculty of Applied Marine Science, Cheju National University) ;
  • Cheong, Jae-Hun (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Choi, Il-Whan (Department of Microbiology, College of Medicine and Center for Viral Disease Research, Inje University) ;
  • Kim, Se-Kwon (Department of Chemistry and Marine Bioprocess Research Center, Pukyong National University) ;
  • Moon, Sung-Kwon (Department of Food and Biotechnology, Chungju National University) ;
  • Kang, Ho-Sung (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School)
  • Published : 2008.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Streptochlorin is a small molecule isolated from marine Streptomyces sp. that is known to have antiangiogenic and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death, using a human hepatocarcinoma Hep3B cell line. The results of this study demonstrated that streptochlorin mediates ROS production, and that this mediation is followed by a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\Psi}_m$), activation of caspase-3, and downregulation of antiapoptotic Bcl-2 protein. The quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the streptochlorin-induced apoptosis effects via inhibition of ROS production, MMP collapse, and the subsequent activation of caspase-3. These observations clearly indicate that ROS are involved in the early molecular events in the streptochlorin-induced apoptotic pathway. Taken together, our data imply that streptochlorin-induced ROS is a key mediator of MMP collapse, which leads to the caspase-3 activation, culminating in apoptosis.

Keywords

References

  1. Boneh, A. 2006. Regulation of mitochondrial oxidative phosphorylation by second messenger-mediated signal transduction mechanisms. Cell. Mol. Life Sci. 63: 1236-1248 https://doi.org/10.1007/s00018-005-5585-2
  2. Cathcart, R., E. Schwiers, and B. N. Ames. 1984. Detection of picomole levels of lipid hydroperoxides using a dichlorofluorescein fluorescent assay. Methods Enzymol. 105: 352-358 https://doi.org/10.1016/S0076-6879(84)05047-3
  3. Choi, I. K., H. J. Shin, H. S. Lee, and H. J. Kwon. 2007. Streptochlorin, a marine natural product, inhibits NF-kB activation and suppresses angiogenesis in vitro. J. Microbiol. Biotechnol. 17: 1338-1343
  4. Chowdhury, I., B. Tharakan, and G. K. Bhat. 2006. Current concepts in apoptosis: The physiological suicide program revisited. Cell. Mol. Biol. Lett. 11: 506-525 https://doi.org/10.2478/s11658-006-0041-3
  5. Darzynkiewicz, Z., E. Bedner, T. Traganos, and T. Murakami. 1998. Critical aspects in the analysis of apoptosis and necrosis. Hum. Cell 11: 3-12
  6. Fulda, S. and K. M. Debatin. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25: 4798-4811 https://doi.org/10.1038/sj.onc.1209608
  7. Ghobrial, I. M., T. E. Witzig, and A. A. Adjei. 2005. Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin. 55: 178-194 https://doi.org/10.3322/canjclin.55.3.178
  8. Gurtu, V., S. R. Kain, and G. Zhang. 1997. Fluorometric and colorimetric detection of caspase activity associated with apoptosis. Anal. Biochem. 251: 98-102 https://doi.org/10.1006/abio.1997.2220
  9. Kroemer, G., L. Galluzzi, and C. Brenner. 2007. Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87: 99-163 https://doi.org/10.1152/physrev.00013.2006
  10. Lazebnik, Y. A., S. H. Kaufmann, S. Desnoyers, G. G. Poirier, and W. C. Earnshaw. 1994. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371: 346-347 https://doi.org/10.1038/371346a0
  11. Mohamad, N., A. Gutierrez, M. Nunez, C. Cocca, G. Martin, G. Cricco, V. Medina, E. Rivera, and R. Bergoc. 2005. Mitochondrial apoptotic pathways. Biocell 29: 149-161
  12. Montague, J. W. and J. A. Cidlowski. 1996. Cellular catabolism in apoptosis: DNA degradation and endonuclease activation. Experientia 52: 957-962 https://doi.org/10.1007/BF01920104
  13. Orrenius, S., V. Gogvadze, and B. Zhivotovsky. 2007. Mitochondrial oxidative stress: Implications for cell death. Annu. Rev. Pharmacol. Toxicol. 47: 143-183 https://doi.org/10.1146/annurev.pharmtox.47.120505.105122
  14. Proksch, P., R. A. Edrada, and R. Ebel. 2002. Drugs from the seas - current status and microbiological implications. Appl. Microbiol. Biotechnol. 59: 125-134 https://doi.org/10.1007/s00253-002-1006-8
  15. Schweder, T., U. Lindequist, and M. Lalk. 2005. Screening for new metabolites from marine microorganisms. Adv. Biochem. Eng. Biotechnol. 96: 1-48
  16. Shin, H. J., H. S. Jeong, H. S. Lee, S. K. Park, H. M. Kim, and H. J. Kwon. 2007. Isolation and structure determination of streptochlorin, an antiproliferative agent from a marine-derived Streptomyces sp. 04DH110. J. Microbiol. Biotechnol. 17: 1403-1406
  17. Singh, S. B. and F. Pelaez. 2008. Biodiversity, chemical diversity and drug discovery. Prog. Drug Res. 65: 143-174
  18. Yin, X. M. 2000. Signal transduction mediated by Bid, a prodeath Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res. 10: 161-167 https://doi.org/10.1038/sj.cr.7290045
  19. Zafarullah, M., W. Q. Li, J. Sylvester, and M. Ahmad. 2003. Molecular mechanisms of N-acetylcysteine actions. Cell. Mol. Life Sci. 60: 6-20 https://doi.org/10.1007/s000180300001

Cited by

  1. Antitumor Compounds from Marine Actinomycetes vol.7, pp.2, 2009, https://doi.org/10.3390/md7020210
  2. Cisplatin induces production of reactive oxygen species via NADPH oxidase activation in human prostate cancer cells vol.45, pp.9, 2008, https://doi.org/10.3109/10715762.2011.591391
  3. A Concise and Rapid Approach to the Marine Natural Product Streptochlorin and its Analogues vol.34, pp.2, 2013, https://doi.org/10.5012/bkcs.2013.34.2.357
  4. Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma vol.9, pp.None, 2015, https://doi.org/10.2147/dddt.s80205
  5. Ocean Dwelling Actinobacteria as Source of Antitumor Compounds vol.59, pp.None, 2008, https://doi.org/10.1590/1678-4324-2016160055
  6. Efficient Preparation of Streptochlorin from Marine Streptomyces sp. SYYLWHS-1-4 by Combination of Response Surface Methodology and High-Speed Counter-Current Chromatography vol.21, pp.6, 2016, https://doi.org/10.3390/molecules21060693
  7. Pharmacokinetics and Metabolism of Streptochlorin and Its Synthetic Derivative, 5-Hydroxy-2′-isobutyl Streptochlorin, in Mice vol.41, pp.3, 2008, https://doi.org/10.1248/bpb.b17-00654