Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma.
BACKGROUND
Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma.


METHODS
The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo.


RESULTS
The IC50 values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 mug/ml, respectively. TGA induced G0/G1 cell cycle arrest at lower concentration (25 mug/ml), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 mug/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner.


CONCLUSIONS
TGA may potentially find use as a new therapy for the treatment of hepatoma.
Tian
Ze
Z
Children's Hospital Informatics Program at Harvard-MIT Division of Health Sciences and Technology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA. ze.tian@childrens.harvard.edu
Si
Jianyong
J
Chang
Qi
Q
Zhou
Liang
L
Chen
Shilin
S
Xiao
Peigen
P
Wu
Erxi
E
D000818:Animals; D017304:Annexin A5 / Q000187:drug effects / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D031885:Cimicifuga / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D009368:Neoplasm Transplantation; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein