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Surfactin Induces Apoptosis and G2/M Arrest in Human Breast Cancer MCF-7 Cells Through Cell Cycle Factor Regulation

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Abstract

Surfactin, purified from Bacillus subtilis natto TK-1, inhibited proliferation of human breast cancer MCF-7 cells in a dose- and time-dependent manner, with IC50 at 24, 48, and 72 h of 82.6, 27.3, and 14.8 μM, respectively. Surfactin-induced cell death was considered to be apoptotic by observing the typical apoptotic morphological change by acridine orange/ethidium bromide staining and Transferase-mediated dUTP Nick End-labeling assay. [Ca2+]i measurement revealed that surfactin induced a sustained increase in concentration of intracellular [Ca2+]i. Flow cytometric analysis also demonstrated that surfactin caused time-dependent apoptosis of MCF-7 cells through cell arrest at G2/M phase. Western blot revealed that surfactin induced accumulation of the tumor suppressor p53 and cyclin kinase inhibitor p21waf1/cip1, and inhibited the activity of the G2-specific kinase, cyclin B1/p34cdc2. Based on our findings, surfactin inhibited proliferation in MCF-7 cells by inducing apoptosis and the elevation of [Ca2+]i may play an important role in the apoptosis. The mechanism which surfactin caused G2/M arrest seems to be through cell cycle factor regulation.

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References

  1. Kameda, Y., Oira, S., Matsui, K., & Hase, T. (1974). Anti-tumor activity of Bacillus natto. V. Isolation and characterization of surfactin in the culture medium of Bacillus natto KMD 2311. Chemical and Pharmaceutical Bulletin, 22, 938–944.

    CAS  Google Scholar 

  2. Ahimou, F., Jacques, P., & Deleu, M. (2001). Surfactin and iturin A effects on Bacillus subtilis surface hydrophobicity. Enzyme and Microbial Technology, 27, 749–754.

    Article  Google Scholar 

  3. Kim, K., Jung, S. Y., Lee, D. K., Jung, J. K., Park, J. K., Kim, D. K., et al. (1998). Suppression of inflammatory responses by surfactin, a selective inhibitor of platelet cytosolic phospholipase A2. Biochemical Pharmacology, 55, 975–985.

    Article  CAS  PubMed  Google Scholar 

  4. Kikuchi, T., & Hasumi, K. (2002). Enhancement of plasminogen activation by surfactin C: Augmentation of fibrinolysis invitro and in vivo. Biochimica et Biophysica Acta, 1596, 234–245.

    CAS  PubMed  Google Scholar 

  5. Singh, P., & Cameotra, S. S. (2004). Potential applications of microbial surfactants in biomedical sciences. Trends in Biotechnology, 22, 142–146.

    Article  CAS  PubMed  Google Scholar 

  6. Vollenbroich, D., Pauli, G., Ozel, M., & Vater, J. (1997). Antimycoplasma properties and applications in cell culture of surfactin, a lipopeptide antibiotic from Bacillus subtilis. Applied and Environmental Microbiology, 63, 44–49.

    CAS  PubMed  Google Scholar 

  7. Cao, X. H., Liao, Z. Y., Wang, C. L., Cai, P., Yang, W. Y., Lu, M. F., et al. (2009). Purification and anti-tumor activity of a lipopeptide biosurfactant produced by Bacillus natto TK-1. Biotechnology and Applied Biochemistry, 52, 97–106.

    Article  CAS  PubMed  Google Scholar 

  8. Kalai, M., Lamkanfi, M., Denecker, L., Boogmans, M., Lippens, S., Meeus, A., et al. (2003). Regulation of the expression and processing of caspase-12. Journal of Cell Biology, 162, 457–467.

    Article  CAS  PubMed  Google Scholar 

  9. Reed, J. (2001). Apoptosis-regulating proteins as targets for drug discovery. Trends in Molecular Medicine, 7, 314–319.

    Article  CAS  PubMed  Google Scholar 

  10. Reed, J. (2003). Apoptosis-targeted therapies for cancer. Cancer Cell, 3, 17–22.

    Article  CAS  PubMed  Google Scholar 

  11. Sergeev, I. N. (2005). Calcium signaling in cancer and vitamin D. Journal of Steroid Biochemistry and Molecular Biology, 97, 145–151.

    Article  CAS  PubMed  Google Scholar 

  12. Ye, J. L., Mao, W. P., Wu, A. L., Zhang, N. N., Zhang, C., Yu, Y. J., et al. (2007). Cadmium-induced apoptosis in human normal liver L-02 cells by acting on mitochondria and regulating Ca2+ signals. Environmental Toxicology and Pharmacology, 24, 45–50.

    Article  Google Scholar 

  13. Sergeev, I. N., Li, S. M., Colby, J. L., Ho, C. T., & Dushenkov, S. (2006). Polymethoxylated flavones induce Ca2+-mediated apoptosis in breast cancer cells. Life Sciences, 80, 245–253.

    Article  CAS  PubMed  Google Scholar 

  14. Antonella, M., Francesca, B., Claudia, B., Ludovica, G., Antonella, T., Simona, B., et al. (2006). Conjugated linoleic acid induces apoptosis in MDA-MB-231 breast cancer cells through ERK/MAPK signalling and mitochondrial pathway. Cancer Letters, 234, 149–157.

    Article  Google Scholar 

  15. Danica, R., Christine, M. C., Tagvor, G. N., Motoyasu, S., Matthew, D. R., Suzanne, D. C., et al. (2003). Epidermal growth factor inhibition of c-Myc-mediated apoptosis through Akt and Erk involves Bcl-xL upregulation in mammary epithelial cells. Experimental Cell Research, 287, 397–410.

    Article  Google Scholar 

  16. Vousden, K. H., & Lu, X. (2002). Live or let die: the cell’s response to p53. Nature Reviews Cancer, 2, 594–604.

    Article  CAS  PubMed  Google Scholar 

  17. Yang, F., von Knethen, A., & Brune, B. (2000). Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21WAF1/CIP1. Journal of Leukocyte Biology, 68, 916–922.

    CAS  PubMed  Google Scholar 

  18. Charrier-Savournin, F. B., Chateau, M. T., Gire, V., Sedivy, J., Piette, J., & Dulic, V. (2004). p21-Mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress. Molecular Biology of the Cell, 15, 3965–3976.

    Article  CAS  PubMed  Google Scholar 

  19. Liang, Y. C., Tsai, S. H., Chen, L., Lin-Shiau, S. Y., & Lin, J. K. (2003). Esveratrol-induced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells. Biochemical Pharmacology, 65, 1053–1060.

    Article  CAS  PubMed  Google Scholar 

  20. Takizawa, C. G., & Morgan, D. O. (2000). Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Current Opinion in Cell Biology, 12, 658–665.

    Article  CAS  PubMed  Google Scholar 

  21. Shukla, S., & Gupta, S. (2007). Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle, 6, 1102–1114.

    CAS  PubMed  Google Scholar 

  22. Kern, J. C., & Kehrer, J. P. (2002). Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chemico-Biological Interactions, 139, 79–95.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang, G. S., Zhou, G. B., & Dai, C. W. (2004). Upregulation and activation of caspase-3 or caspase-8 and elevation of intracellular free calcium mediated apoptosis of indomethacin-induced K562 cells. Chinese Medical Journal, 117, 978–984.

    CAS  PubMed  Google Scholar 

  24. Wang, C. L., Ng, T. B., Yuan, F., Liu, Z. K., & Liu, F. (2007). Induction of apoptosis in human leukemia K562 cells by cyclic lipopeptide from Bacillus subtilis natto T-2. Peptides, 28, 1344–1350.

    Article  PubMed  Google Scholar 

  25. Kaufmann, S. H., & Hengartner, M. O. (2001). Programmed cell death: Alive and well in the new millennium. Trends in Cell Biology, 11, 526–534.

    Article  CAS  PubMed  Google Scholar 

  26. Lee, E. O., Kwon, B. M., Song, G. Y., Chae, C. H., Kim, H. M., Shim, I. S., et al. (2004). Heyneanol A induces apoptosis via cytochrome c release and caspase activation in human leukemic U937 cells. Life Sciences, 74, 2313–2326.

    Article  CAS  PubMed  Google Scholar 

  27. Woo, S. H., Park, I. C., Park, M. J., Lee, H. C., Lee, S. J., Chun, Y. J., et al. (2002). Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells. International Journal of Oncology, 21, 57–63.

    CAS  PubMed  Google Scholar 

  28. Anuradha, C. D., Kanno, S., & Hirano, S. (2001). Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells. Free Radical Biology and Medicine, 31, 367–373.

    Article  CAS  PubMed  Google Scholar 

  29. Hsu, S. S., Huang, C. J., Cheng, H. H., Chou, C. T., Lee, H. Y., Wang, J. L., et al. (2007). Anandamide-induced Ca2+ elevation leading to p38 MAPK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells. Toxicology, 231, 21–29.

    Article  CAS  PubMed  Google Scholar 

  30. Agrawal, S., Agarwal, M. L., Chatterjee-Kishore, M., Stark, G. R., & Chisolm, G. M. (2005). Stat1-dependent, p53-independent expression of p21(waf1) modulates oxysterol-induced apoptosis. Molecular and Cellular Biology, 22, 1981–1992.

    Article  Google Scholar 

  31. Mahyar-Roemer, M., & Roemer, K. (2001). p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents. Oncogene, 20, 3387–3398.

    Article  CAS  PubMed  Google Scholar 

  32. Agarwal, M. L., Agarwal, A., Taylor, W. R., & Stark, G. R. (1995). p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proceedings of the National Academy of Sciences USA, 92, 8493–8497.

    Article  CAS  Google Scholar 

  33. Hartwell, L. H., & Kastan, M. B. (1994). Cell cycle control and cancer. Science, 266, 1821–1828.

    Article  CAS  PubMed  Google Scholar 

  34. Molinari, M. (2000). Cell cycle checkpoints and their inactivation in human cancer. Cell Proliferation, 33, 261–274.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge with thanks the funding by National Natural Science Funds of China (Grant No. 20676103) and National High Tech Research and Development Program (863) (Grant No. 2007AA10Z319).

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Authors and Affiliations

  1. Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin, 300457, China

    Xiaohong Cao, A. H. Wang, R. Z. Jiao, C. L. Wang, D. Z. Mao, L. Yan & B. Zeng

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  1. Xiaohong Cao
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  2. A. H. Wang
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  3. R. Z. Jiao
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  4. C. L. Wang
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Correspondence to Xiaohong Cao.

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Cao, X., Wang, A.H., Jiao, R.Z. et al. Surfactin Induces Apoptosis and G2/M Arrest in Human Breast Cancer MCF-7 Cells Through Cell Cycle Factor Regulation. Cell Biochem Biophys 55, 163–171 (2009). https://doi.org/10.1007/s12013-009-9065-4

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