Apoptosis-inducing activity of cisplatin (CDDP) against human hepatoma and oral squamous cell carcinoma cell lines.
The sensitivity of human hepatoma (HepG2) and oral squamous cell carcinoma (HSC-2) cell lines against various apoptosis-inducing agents was compared. HepG2 cells were generally more resistant to an oxidant (H2O2), antioxidants (sodium ascorbate, gallic acid, epigallocatechin gallate) and anticancer drugs (doxorubicin, methotrexate, cisplatin (CDDP), etoposide, 5-fluoro-2,4(1H,3H)-pyrimidinedione (5-FU), peplomycin sulfate) as compared to HSC-2 cells. Lower concentrations of CDDP, but not other anticancer drugs, induced comparable cytostatic effects on both HSC-2 and HepG2 cells. CDDP induced internucleosomal DNA fragmentation and activation of caspases 3, 8 and 9 in HepG2 cells. On the other hand, CDDP did not induce DNA fragmentation and activated caspase 3 only marginally in HSC-2 cells. Combination treatment with CDDP (10 microM) and 5-FU (100 microM) additively activated all three caspases in HepG2 cells, but not in HSC-2 cells. The present study demonstrated the chemotherapeutic potential of combined treatment of CDDP and 5-FU against hepatoma cells and the considerable variation of drug sensitivity between cancer cell lines.
Okamura
Masahiko
M
First Department of Oral Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Hashimoto
Ken
K
Shimada
Jun
J
Sakagami
Hiroshi
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D020169:Caspases; D002945:Cisplatin; D005472:Fluorouracil