Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells.
Matrine is a component of the traditional Chinese medical herb Sophora flavescens Ait, which is widely used to treat diseases such as viral hepatitis, cardiac arrhythmia and skin inflammations. As indicated by previous reports, the molecular mechanism of matrine's anti-cancer effect has been poorly clarified. In this study, we used both in vitro and in vivo models to investigate matrine's antitumor effect and its possible molecular mechanisms. Murine hepatocellular carcinoma H22 cells were cultured in the presence of matrine at various concentrations (0.2 - 2.0 mg/mL). A dose-dependent antiproliferation effect was observed. The 50 % inhibitory concentration (IC (50)) was 0.6 mg/mL. Antiproliferation effects of matrine were associated with an increase in cells arrested in the G (1) phase of the cell cycle. Morphological changes, flow cytometric analysis and expression of the proapoptotic protein Bax indicated that this anticancer effect was mediated via apoptosis. In vivo antitumor efficacy was evaluated following S. C. inoculation of H22 cells in BALB/c mice. Matrine administrated I. P. resulted in strong in vivo anticancer activity. Our results showed that seven doses of matrine at 50 mg/kg/dose inhibited 60.7 % of tumor growth. Transmission electron microscope (TEM) analysis and histoimmunochemical staining for Bcl-2 and Bax proteins also indicated induction of apoptosis in tumor tissues by matrine. Taken together, our results demonstrate that matrine possesses strong antitumor activities in vitro and in vivo. Inhibition of cell proliferation and induction of apoptosis are the likely mechanisms responsible for matrine's antitumor activities.
Ma
Lingdi
L
Center Laboratory, The Second Changzhou People's Hospital, The Affiliated Hospital of the Nanjing Medical University, Changzhou, P. R. China.
Wen
Shihong
S
Zhan
Yan
Y
He
Yujuan
Y
Liu
Xiaoshan
X
Jiang
Jikai
J
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology / Q000627:therapeutic use*; D029909:Sophora / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; D051028:bcl-2-Associated X Protein; D000093842:Matrines