Cytotoxic activity and cytostatic mechanism of novel 2-arylbenzo[b]furans.
The aims of this study were to screen cytotoxic compounds from 14 newly-synthesized 2-arylbenzo[b]furans and explore their mechanisms of action. Cytotoxicity was determined by the MTT method. Cell-cycle distribution was detected by flow cytometry. Wright-Giemsa staining was performed to demonstrate the morphological features of cells in mitotic phase. Polymerization of tubulin was detected by tubulin assembly assay, and the cellular microtubule network was observed by immunocytochemical study. Among the 14 compounds screened, 4-formyl-2-(4-hydroxy-3-methoxyphenyl)-5-(2-methoxycarbonyethyl)-7-methoxy-benzo[b]furan (ERJT-12) showed significant cytotoxicity. Our results demonstrated that ERJT-12 exhibited anti-cancer activity in a variety of tumour cell lines with an IC50 value (concentration resulting in 50% inhibition of cell growth) of 5.75 approximately 17.29 microM. Cell cycle analysis showed a concentration-dependent accumulation of tumour cells in G2/M phase after treatment with ERJT-12. Further investigation indicated that ERJT-12 blocked the cell cycle in M phase, with separation and dispersion of chromosomes. ERJT-12 inhibited tubulin polymerization in-vitro. Changes of the cellular microtubule network caused by ERJT-12 were also detected, which were similar to the changes caused by colchicine. These results suggested that the anti-cancer activity of ERJT-12 is worth further investigation.
Yang
Hua
H
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, P. R. China.
Pang
Ji-Yan
JY
Cai
Yu-Chen
YC
Xu
Zun-Le
ZL
Xian
Li-Jian
LJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology*
C515704:4-formyl-2-(4-hydroxy-3-methoxyphenyl)-5-(2-methoxycarbonyethyl)-7-methoxy-benzo(b)furan; D000970:Antineoplastic Agents; D001572:Benzofurans; D003603:Cytotoxins; D014404:Tubulin; D050257:Tubulin Modulators