Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth.
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 microM, 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 microM 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.
Ping
Szu-Yuan
SY
Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Hour
Tzyh-Chyuan
TC
Lin
Shinne-Ren
SR
Yu
Dah-Shyong
DS
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011759:Pyrrolidines / Q000008:administration & dosage; D013859:Thiocarbamates / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
D000970:Antineoplastic Agents; D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; D014810:Vitamin E; C020972:pyrrolidine dithiocarbamic acid; D002392:Catechin; C045651:epigallocatechin gallate; D019833:Genistein; D017239:Paclitaxel