Sensitization by glycerol for CDDP-therapy against human cultured cancer cells and tumors bearing mutated p53 gene.
To clarify effective chemotherapeutic regimens against cancer, we examined the effects of glycerol on apoptosis induced by CDDP treatment using cultured human cancer cells (in vitro) and transplanted tumor in mice (in vivo). Human tongue cell carcinoma (SAS) cells transfected with mutated p53 gene (SAS/m p53) showed CDDP-resistance compared with the cells with neo control gene (SAS/ neo). When those cultured cells were pre-treated with glycerol, CDDP-induced apoptosis was enhanced by glycerol in SAS/m p53 cells but not in SAS/ neo cells. In tumor-transplanted mice, the glycerol treatment to tumors enhanced growth delay induced by CDDP in mp53 tumors transplanted with SAS/m p53 cells, but not in wtp53 tumors transplanted with SAS/ neo cells. When transplanted tumors were treated with CDDP alone, the cells positive for active caspase-3, 85 kDa PARP and apoptosis were observed by immunohistochemical staining in wtp53 tumors but not in mp53 tumors. When the tumors were treated with CDDP combined with glycerol, positive cells were observed not only in wtp53 tumors but also in mp53 tumors. These results showed that the CDDP-induced growth inhibition of the tumors is p53 -dependent and that the enhanced growth delay by glycerol may be due to the increased apoptosis. Glycerol might be available for cancer chemotherapy in patients with mp53 tumors.
Yuki
K
K
Department of Otorhinolaryngology, Nara Medical University School of Medicine, Kashihara, Nara, 634-8521, Japan.
Takahashi
A
A
Ota
I
I
Ohnishi
K
K
Yasumoto
J
J
Yane
K
K
Kanata
H
H
Okamoto
N
N
Hosoi
H
H
Ohnishi
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016158:Genes, p53; D005990:Glycerol / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014062:Tongue Neoplasms / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D020169:Caspases; D005990:Glycerol; D002945:Cisplatin