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Article

Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo

  • Authors:
    • Jie Lin
    • Yongji Wu
    • Dajun Yang
    • Yongqiang Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, P.R. China, Ascenta Therapeutics, Inc., San Diego, CA, USA
  • Pages: 731-738
    |
    Published online on: May 23, 2013
       https://doi.org/10.3892/or.2013.2489
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Abstract

Gossypol is a naturally occurring polyphenolic compound extracted from cotton plants. Recent studies revealed that gossypol is a non-peptidic small molecule inhibitor of Bcl-2/Bcl-xl. The aim of the present study was to investigate the induction of apoptosis and antitumor effects of gossypol acetate in multiple myeloma and the possible mechanism(s) of action. Our results showed that gossypol acetate resulted in a dose- and time-dependent inhibition of multiple myeloma cell proliferation, with an IC50 value to both U266 and Wus1 cells at 2.4, 2.2 µM at 48 h after treatment. Gossypol acetate effectively induced the apoptosis of multiple myeloma cells as demonstrated by typical morphological changes, DNA ladder formation and increase in the percentage of cells in subdiploid peak. Furthermore, colorimetric assays showed activation of both caspase-3 and caspase-9. Bcl-2 and Bcl-xl expression was decreased by 86.5±1.2% and 35.9±3.6%, respectively, after treatment with gossypol acetate at 25 µmol/l for 24 h. Preliminary studies in vivo showed that a growth inhibition (T/C) of 30.9% (gossypol acetate 40 mg/kg) was obtained in Balb/C mice bearing Wus1 cells. In addition, there was no body weight loss for the treated group in comparison with the vehicle mice. Our results demonstrated that the potent inhibitor of Bcl-2 and Bcl-xl gossypol acetate had significant antiproliferative and antiapoptotic effects on multiple myeloma cells in vitro and in vivo. Gossypol acetate may represent a promising new anticancer agent with a novel molecular mechanism and warrants further investigation as a single agent, or in combination with other chemotherapeutics, for human multiple myeloma with Bcl-2 overexpression.
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Copy and paste a formatted citation
Spandidos Publications style
Lin J, Wu Y, Yang D and Zhao Y: Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol Rep 30: 731-738, 2013.
APA
Lin, J., Wu, Y., Yang, D., & Zhao, Y. (2013). Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncology Reports, 30, 731-738. https://doi.org/10.3892/or.2013.2489
MLA
Lin, J., Wu, Y., Yang, D., Zhao, Y."Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo". Oncology Reports 30.2 (2013): 731-738.
Chicago
Lin, J., Wu, Y., Yang, D., Zhao, Y."Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo". Oncology Reports 30, no. 2 (2013): 731-738. https://doi.org/10.3892/or.2013.2489
Copy and paste a formatted citation
x
Spandidos Publications style
Lin J, Wu Y, Yang D and Zhao Y: Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol Rep 30: 731-738, 2013.
APA
Lin, J., Wu, Y., Yang, D., & Zhao, Y. (2013). Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncology Reports, 30, 731-738. https://doi.org/10.3892/or.2013.2489
MLA
Lin, J., Wu, Y., Yang, D., Zhao, Y."Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo". Oncology Reports 30.2 (2013): 731-738.
Chicago
Lin, J., Wu, Y., Yang, D., Zhao, Y."Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo". Oncology Reports 30, no. 2 (2013): 731-738. https://doi.org/10.3892/or.2013.2489
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