Matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo cells by inactivating Akt pathway.
The present study has investigated the anti-tumor activity and the underlying mechanisms of matrine on human colon cancer LoVo cells. Matrine inhibited the proliferation of the cells in dose- and time-dependent manners. The concentration required for 50 % inhibition (IC50) was 1.15, 0.738, and 0.414 mg/ml, when cell were incubated with matrine for 24, 48, and 72 h, respectively. Matrine induced cell cycle arrest at G1 phase by downregulating cyclin D1 and upregulating p27 and p21. Matrine induced cell apoptosis by reducing the ratio of Bcl-2/Bax and increasing the activation of caspase-9 in a dose-dependent manner. Matrine displayed its anti-tumor activity by inactivating Akt, the upstream factor of the above proteins. Matrine significantly reduced the protein levels of pAkt, and increased the protein levels of other downstream factors, pBad and pGSK-3β. Specific inhibition of pAkt induced cell apoptosis, and synergized with matrine to inhibit the proliferation of LoVo cells; whereas activation of Akt neutralized the inhibitory effect of matrine on cell proliferation. The present study has demonstrated that matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo cells by inactivating Akt pathway, indicating matrine may be a potential anti-cancer agent for colon cancer.
Department of Pathology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Shujun
S
Zhang
Binglin
B
Cheng
Hali
H
Li
Wei
W
Xu
Bo
B
Zhai
Shangha
S
Pan
Lei
L
Wang
Ming
M
Liu
Xueying
X
Sun
D000470:Alkaloids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; D000093842:Matrines