Phorbol myristate induces apoptosis of taxol-resistant sarcoma cells in vitro.
Taxol was found to induce polyploidization and apoptosis in cultured methylcholanthrene-induced sarcoma cells (Meth-A cells), but some of the cells in G1 phase were not affected. We refer to these cells as taxol-resistant cells. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) regulator, was used to test the taxol-resistant cells. Many of the taxol-resistant cells disappeared after treatment with taxol in the presence of PMA. To explore the mechanism of this effect, we employed flow cytometry to determine levels of p53, p21, bcl-2 and caspase proteins in the taxol-resistant cells, and found that the expression of the bcl-2 protein was markedly decreased and the expression of the caspase protein markedly increased after treatment with taxol in the presence of PMA. These findings suggest that PMA enhances the sensitivity of taxol-resistant cells to taxol, and taxol treatment in the presence of PMA induces the apoptosis of taxol-resistant cells by inhibiting the expression of the bcl-2 protein and increasing the expression of the caspase protein.
Zong
Zhi-ping
ZP
Medical Research Institute, Division of Basic Science, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-0293, Japan. zong3961@kanazawa-med.ac.jp
Matsui
Shinobu
S
Katsuda
Shogo
S
Han
Jian-feng
JF
Fujikawa-Yamamoto
Kohzaburo
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*; D011123:Polyploidy; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000473:pathology*; D013534:Survival; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004247:DNA; D020169:Caspases; D015689:Oncogene Protein p21(ras); D013755:Tetradecanoylphorbol Acetate; D017239:Paclitaxel