[In vitro inhibitory effect of dibenzoxanthene CY-B12 on proliferation of tumor cell lines and its possible mechanisms].
OBJECTIVE
CY-B12, a new dibenzon-xanthene, has been synthesized recently. This study was to investigate the in vitro antiproliferative activity of CY-B12 and its possible mechanisms.


METHODS
The inhibitory effects of CY-B12 on proliferation of gastric carcinoma cell line MGC803, nasopharyngeal carcinoma cell line CNE-2, oral epithelial carcinoma cell line KB-3-1, and lung cancer cell line Glc82 were assessed by MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometry (FCM). Apoptotic morphology of CNE-2 cells was observed under fluorescent microscope after Hoechst33258 staining. The expression of cell cycle-related proteins Cdc25C, Cdc2, and Cyclin B1 were measured by Western blot. DNA damage was detected by single cell gel electrophoresis (SCGE).


RESULTS
CY-B12 obviously inhibited the proliferation of MGC803, CNE-2, KB-3-1, and Glc82 cells; the IC(50) values were 7.51, 9.58, 8.84, and 15.99 micromol/L, respectively. After treatment of CY-B12, CNE-2 cells were arrested at G(2)/M phase; chromatin condensation, apoptotic bodies, and sub-G1 peak were observed in CNE-2 cells. The protein expression of Cdc25C in CNE-2 cells was down-regulated by CY-B12 in a dose-dependent mannerû whereas Cyclin B1 and Cdc2 were up-regulated by low dose of CY-B12, and down-regulated by high dose of CY-B12. CY-B12 induced DNA damage in CNE-2 cells in a dose-dependent manner.


CONCLUSIONS
CY-B12 has potent in vitro antiproliferative activity, which may be exerted through breaking DNA, down-regulating cell cycle-related protein Cdc25C, and inducing cell cycle arrest and apoptosis.
Pu
Xing-Xiang
XX
Skate Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong 510060, P. R. China.
Jiang
Gao-Feng
GF
Chen
Yong
Y
Xu
Zun-Le
ZL
Xian
Li-Jian
LJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D014966:Xanthenes / Q000138:chemical synthesis / Q000494:pharmacology*; D020687:cdc25 Phosphatases / Q000378:metabolism*
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D014966:Xanthenes; C011759:dibenzoxanthenes; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases