Inhibition of alpha(4) integrin mediated adhesion was involved in the reduction of B16-F10 melanoma cells lung colonization in C57BL/6 mice treated with gambogic acid.
Gambogic acid, the major active ingredient of gamboge, has been shown to exhibit anti-cancer activity both in vivo and in vitro. However, its potential activity in tumor metastasis remains unclear. In the present study, we found that gambogic acid strongly inhibited the adhesion of highly metastatic mouse melanoma B16-F10 cells in vitro. Gambogic acid also exhibited significant anti-metastasis activity on the development of in vivo artificial metastases (i.e. following tail vein i.v. injection of the B16-F10 melanoma tumor cells in C57BL/6 mice). Flow cytometric analysis and Western blot showed that gambogic acid inhibited the cell surface expression of alpha(4) integrin, while exhibited negligible effects on the expression of alpha(5) and beta(1) integrin. Thus we concluded for the first time that gambogic acid could inhibit the adhesion and migration of B16-F10 cells in vitro and in vivo, in which down-regulation of alpha(4) integrin expression was involved.
Jiangsu Key Laboratory of Carcinogenesis and intervention (China Pharmaceutical University), Nanjing, PR China.
Jie
J
Zhao
Qi
Q
Qi
Yong
Y
Yang
Hong-Yan
HY
Gu
Na
N
Lu
Wei
W
Liu
Wei
W
Wang
Lei
L
Qiang
Ling-Bo
LB
Zhang
Qi-Dong
QD
You
Qing-Long
QL
Guo
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D020128:Inhibitory Concentration 50; D039441:Integrin alpha4 / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D044004:Xanthones / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D044004:Xanthones; D039441:Integrin alpha4; C052659:gambogic acid