Urologic Oncology: Seminars and Original Investigations
Volume 28, Issue 2 , Pages 170-179, March 2010

Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth

  • Szu-Yuan Ping, M.A.

      Affiliations

    • Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan, Republic of China
    • S.-Y.P. and T.-C.H. contributed equally to this work.
  • ,
  • Tzyh-Chyuan Hour, Ph.D.

      Affiliations

    • Institute of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
    • Center of Excellent for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
    • S.-Y.P. and T.-C.H. contributed equally to this work.
  • ,
  • Shinne-Ren Lin, Ph.D.

      Affiliations

    • Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
  • ,
  • Dah-Shyong Yu, M.D., Ph.D.

      Affiliations

    • Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital and Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
    • Corresponding Author InformationCorresponding author. Tel.: +886-2-8792-7008; fax: +886-2-8792-7009

Received 23 May 2008; accepted 10 July 2008. published online 26 September 2008.

Abstract 

Taxanes are chemotherapeutic agents commonly used to treat various carcinomas. Dietary antioxidants, such as vitamin E, green tea extracts, and isoflavones have been used against prostate cancer, and exhibit anticancer effects both in vitro and in vivo. We evaluated the combined effect of taxol (paclitaxel) with pyrrolidine dithiocarbamate, vitamin E, epigallocatechin gallate, and genistein in killing hormone-refractory prostate cancer cells. Those agents were tested on the hormone-refractory prostate cancer cell line PC-3, and the viability of the cells was determined using MTT {3 (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium} assay after drug treatment. PC-3 cells were sensitive to these drugs with 50% inhibitory concentrations of 0.1, 23, 220, 1122, and 260 μM, for taxol, pyrrolidine dithiocarbamate, epigallocatechin gallate, genistein, and vitamin E, respectively. Genistein, pyrrolidine dithiocarbamate, and epigallocatechin gallate showed synergistic cytotoxicity to PC-3 cells when combined with 0.01 μM taxol. Only high concentration of vitamin E showed a synergistic effect with this dose of taxol. Further study revealed that 3 combinations could induce sub-G1 phase of cell cycle, induce apoptosis, and increase caspase activity and decrease Bcl-2 expression simultaneously. In conclusion, in addition to vitamin E, incorporation of these antioxidants with taxan-based cytotoxic therapies offers encouraging strategies for combating hormone-refractory prostate cancers.

Keywords: Taxol, Antioxidants, Drug synergism, Hormone-refractory prostate cancer

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 This project was supported by the National Science Council of Republic of China (NSC 90-2314-B-037-118) and the Center of Excellence for Environmental Medicine, Kaohsiung Medical University (KMU-EM-97-2.1b).

PII: S1078-1439(08)00161-0

doi:10.1016/j.urolonc.2008.07.003

Urologic Oncology: Seminars and Original Investigations
Volume 28, Issue 2 , Pages 170-179, March 2010