Geraniin induces apoptosis of human breast cancer cells MCF-7 via ROS-mediated stimulation of p38 MAPK.
Geraniin, a typical ellagitannin isolated from Phyllanthus urinaria Linn, has been found to possess a range of bioactive properties. In the present study, we found that Geraniin showed potent anti-proliferative effects on human breast cancer MCF-7 cells. The IC50 values were 9.94, 17.98 and 42.32 µM after 72-, 48- and 24-h treatment, respectively. Meanwhile, Geraniin could remarkably disrupt mitochondrial membrane potential and arrest S phase cell cycle. Western-blot analysis showed that Geraniin induced phosphorylation of the anti-apoptotic Bcl-2, and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3 in MCF-7 cells. Moreover, Geraniin treatment activated p38 mitogen-activated protein kinase (p38 MAPK) and the effect was blunted in MCF-7 cells with the treatment of a specific p38 inhibitor SB203580. Geraniin could generate intracellular reactive oxygen species (ROS), activate p38 MAPK then induce the apoptosis in MCF-7 cells, such phenomena was abrogated by pretreatment with N-acetyl-l-cysteine. In general, these results support the conclusion that Geraniin-induced apoptosis is mediated via ROS-mediated stimulation of p38 MAPK signaling.
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Jia-Wen
JW
Zhai
d Peking University People's Hospital , Beijing , PR China.
Chang
C
Gao
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Wei-Dong
WD
Ma
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Wei
W
Wang
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Li-Ping
LP
Yao
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Xin-Xin
XX
Xia
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Meng
M
Luo
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Yuan-Gang
YG
Zu
a Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University , Harbin , PR China .|b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin , PR China .|c Collaborative Innovation Center for Development and Utilization of Forest Resources, Northeast Forestry University , Harbin , PR China .
Yu-Jie
YJ
Fu
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D047348:Hydrolyzable Tannins; D017382:Reactive Oxygen Species; C024603:Geraniin; D048051:p38 Mitogen-Activated Protein Kinases
Apoptosis; MCF-7 cells; ROS; geraniin; mitochondrial; p38 MAPK