Microtubule depolymerization and phosphorylation of c-Jun N-terminal kinase-1 and p38 were involved in gambogic acid induced cell cycle arrest and apoptosis in human breast carcinoma MCF-7 cells.
Gambogic acid (GA), an ingredient isolated from Garcinia hanburyi, has potent anticancer activity both in vitro and in vivo. In the present study, we examined the effects of GA on intracellular microtubules and reconstituted microtubules in vitro. Immunofluorescence microscopy revealed that 2.5 muM GA caused microtubule cytoskeleton disruption and microtubule depolymerization in human breast carcinoma MCF-7 cells, thereby reducing the amount of polymer form of tubulin and increasing the amount of monomer form of tubulin. We further confirmed that GA could depolymerize microtubule associated protein (MAP)-free microtubules and MAP-rich microtubules in vitro. Thus we suggested that GA-induced G2/M phase cell cycle arrest may be attributed to its depolymerization of microtubules. We also revealed that phosphorylation levels of p38 and c-Jun N-terminal kinase-1 (JNK-1) were increased markedly by GA, resulting in apoptosis of MCF-7 cells. Taken together, our results suggested that GA depolymerized microtubules and elevated the phosphorylation levels of JNK1 and p38, which caused G2/M cell cycle arrest and apoptosis in MCF-7 cells.
Chen
Jing
J
Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), Nanjing, PR China.
Gu
Hong-Yan
HY
Lu
Na
N
Yang
Yong
Y
Liu
Wei
W
Qi
Qi
Q
Rong
Jing-Jing
JJ
Wang
Xiao-Tang
XT
You
Qi-Dong
QD
Guo
Qing-Long
QL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D010766:Phosphorylation; D014404:Tubulin / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D044004:Xanthones; C052659:gambogic acid; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases