Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular carcinoma via regulation of MMP/TIMP balance as therapeutic target.
Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. Thus, the inhibition of invasion and metastasis is of great importance in its therapies. Medicinal plants or ethnopharmacology used in folklore medicine continue to be an important source of discovery and development of novel or potential therapeutic agents for treatment of cancer. Chrysanthemum indicum, one of the medicinal plants or ethnopharmacology, is being used for treatment of many diseases including cancer. However, this plant molecular mechanisms underlining the anti-metastatic effects have not been well documented. In this study, Chrysanthemum indicum ethanolic extract (CIE) significantly suppressed proliferation and invasion of MHCC97H cells, one of the HCC cell lines with high metastatic potential, in a dose-dependent manner. CIE markedly decreased MMP-2 and MMP-9 expression, increased simultaneously TIMP-1, and TIMP-2 expression further restoring their balance in the cancer cells. The present study indicates that CIE reduced MHCC97H cell metastatic capability, in part at least, through decrease of the MMP expression, simultaneous increase of the TIMP expression, further restoring their balance as therapeutic target in HCC. It is suggested that Chrysanthemum indicum is a potential novel therapeutic medicinal plant for treatment of HCC or cancer invasion and metastasis.
Wang
Zhi-Dong
ZD
Department of Surgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi Province, PR China.
Huang
Chen
C
Li
Zong-Fang
ZF
Yang
Jun
J
Li
Bao-Hua
BH
Liang
Rong-Rui
RR
Dai
Zhi-Jun
ZJ
Liu
Zhong-Wei
ZW
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D031202:Chrysanthemum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D019714:Tissue Inhibitor of Metalloproteinases; D000431:Ethanol; D020782:Matrix Metalloproteinases