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Article

Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells

  • Authors:
    • Hyeon Jun Kim
    • Seung Gee Lee
    • Yoon-Jae Kim
    • Ji-Eun Park
    • Kyu Yeol Lee
    • Young Hyun Yoo
    • Jong-Min Kim
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea, Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea, Medical Research Science Center, Dong-A University, Busan 602-714, Republic of Korea, Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714, Republic of Korea
  • Pages: 1985-1992
    |
    Published online on: April 5, 2013
       https://doi.org/10.3892/ijo.2013.1884
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Abstract

Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Although paclitaxel (PCX) has been considered one of the most important cancer chemotherapeutic drugs, the current protocols for OS treatment do not incorporate this agent. Therefore, the purpose of this study was to evaluate the induction of cell death in OS cells after exposure to PCX, to identify the cell death mechanism(s) activated by PCX and to investigate whether autophagy is associated with PCX-induced apoptosis. The results of the present study confirmed that exposure to low PCX concentrations can induce apoptotic cell death in Saos-2 cells; furthermore, caspase-3 activation, PARP degradation and XIAP downregulation were observed in combination with PCX-induced apoptosis. The potential involvement of mitochondrial events (intrinsic apoptotic pathway) in PCX-induced apoptosis in OS cells was verified by the alteration (depolarization) of mitochondrial membrane potential. In addition, pretreatment with 3-methyladenine (3-MA), a specific inhibitor of autophagy, significantly increased PCX-induced apoptotic cell death in Saos-2 cells. The augmentation of PCX-induced apoptosis by 3-MA was accompanied by increase in the cytochrome c release from the mitochondria, caspase-3 activity and XIAP downregulation, which suggests that inhibiting autophagy further stimulates the PCX-induced mitochondrion-related (intrinsic) apoptotic pathway by provoking caspase-3 activation. Thus, autophagy observed during PCX-induced apoptosis in Saos-2 OS cells represents the role of cytoprotection in cellular homeostatic processes. In conclusion, the results of this study revealed that PCX exposure effectively induces OS cell death by apoptosis associated with the mitochondrial-mediated caspase-dependent pathway. PCX can increase autophagic activity and suppressing autophagy enhances PCX-induced apoptosis in OS cells. Therefore, it is suggested that combination treatment involving low-dose PCX therapy and autophagy inhibitor therapy could be an effective and potent strategy for improved chemotherapy for OS in the near future.
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Copy and paste a formatted citation
Spandidos Publications style
Kim HJ, Lee SG, Kim Y, Park J, Lee KY, Yoo YH and Kim J: Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells. Int J Oncol 42: 1985-1992, 2013.
APA
Kim, H.J., Lee, S.G., Kim, Y., Park, J., Lee, K.Y., Yoo, Y.H., & Kim, J. (2013). Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells. International Journal of Oncology, 42, 1985-1992. https://doi.org/10.3892/ijo.2013.1884
MLA
Kim, H. J., Lee, S. G., Kim, Y., Park, J., Lee, K. Y., Yoo, Y. H., Kim, J."Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells". International Journal of Oncology 42.6 (2013): 1985-1992.
Chicago
Kim, H. J., Lee, S. G., Kim, Y., Park, J., Lee, K. Y., Yoo, Y. H., Kim, J."Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells". International Journal of Oncology 42, no. 6 (2013): 1985-1992. https://doi.org/10.3892/ijo.2013.1884
Copy and paste a formatted citation
x
Spandidos Publications style
Kim HJ, Lee SG, Kim Y, Park J, Lee KY, Yoo YH and Kim J: Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells. Int J Oncol 42: 1985-1992, 2013.
APA
Kim, H.J., Lee, S.G., Kim, Y., Park, J., Lee, K.Y., Yoo, Y.H., & Kim, J. (2013). Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells. International Journal of Oncology, 42, 1985-1992. https://doi.org/10.3892/ijo.2013.1884
MLA
Kim, H. J., Lee, S. G., Kim, Y., Park, J., Lee, K. Y., Yoo, Y. H., Kim, J."Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells". International Journal of Oncology 42.6 (2013): 1985-1992.
Chicago
Kim, H. J., Lee, S. G., Kim, Y., Park, J., Lee, K. Y., Yoo, Y. H., Kim, J."Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells". International Journal of Oncology 42, no. 6 (2013): 1985-1992. https://doi.org/10.3892/ijo.2013.1884
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