Tylophorine arrests carcinoma cells at G1 phase by downregulating cyclin A2 expression.
Tylophorine, a representative phenanthroindolizidine alkaloid from Tylophoraindica plants, exhibits anti-inflammatory and anti-cancerous growth activities. However, the underlying mechanisms of its anti-cancer activity have not been elucidated and its effects on cell cycle remain ambiguous. Here, we reveal by asynchronizing and synchronizing approaches that tylophorine not only retards the S-phase progression but also dominantly arrests the cells at G1 phase in HepG2, HONE-1, and NUGC-3 carcinoma cells. Moreover, tylophorine treatment results in down regulated cyclin A2 expression and overexpressed cyclin A2 rescues the G1 arrest by tylophorine. Thus, we are the first to report that the downregulated cyclin A2 plays a vital role in G1 arrest by tylophorine in carcinoma cells.
Wu
Chia-Mao
CM
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 350, Taiwan, ROC.
Yang
Cheng-Wei
CW
Lee
Yue-Zhi
YZ
Chuang
Ta-Hsien
TH
Wu
Pei-Lin
PL
Chao
Yu-Sheng
YS
Lee
Shiow-Ju
SJ
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000037:antagonists & inhibitors* / Q000235:genetics; D056751:Cyclin A2; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007212:Indolizines / Q000494:pharmacology*; D010616:Phenanthrenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D000470:Alkaloids; D000970:Antineoplastic Agents; C503721:CCNA2 protein, human; D019925:Cyclin A; D056751:Cyclin A2; D007212:Indolizines; D010616:Phenanthrenes; C004218:tylophorine