Kaempferol-7-O-beta-D-glucoside (KG) isolated from Smilax china L. rhizome induces G2/M phase arrest and apoptosis on HeLa cells in a p53-independent manner.
Kaempferol-7-O-beta-D-glucoside (KG), a flavonoid glycoside, isolated from Smilax china L. rhizome, displayed marked anticancer activity on a panel of established cancer cells, of which, HeLa human cervix carcinoma cells were the most sensitive. Meanwhile, the cytotoxic effects of KG on normal human cells (HEK293 embryonic kidney cells and L-02 embryonic liver cells) were much smaller than on cancer cells. This work studied the molecular mechanisms underlying KG induced growth inhibition in HeLa cells. The results showed that KG induced G2/M phase growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes, evident DNA fragmentation, increased apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed in HeLa cells treated with KG, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. In summary, KG displayed a significant anti-tumor effect through cell cycle arrest and apoptotic induction in HeLa cells, which suggested that KG might have therapeutic potential against cervix carcinoma.
Xu
Wen
W
State Key Laboratory of Bioreactor Engineering & School of pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237, PR China.
Liu
Jianwen
J
Li
Changlong
C
Wu
He-Zhen
HZ
Liu
Yan-Wen
YW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D006027:Glycosides / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027343:Rhizome / Q000737:chemistry; D032281:Smilax / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D006027:Glycosides; D044949:Kaempferols; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C511993:kaempferol-3-O-(6-trans-caffeoyl)-beta-D-glucopyranosyl-(1- 2)-beta-D-glucopyranoside-7-O-beta-D-glucopyranoside