Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells.
Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. In the present study, we investigated the effects of the PR isoflavones puerarin, daidzein, and genistein on the growth of breast cancer cells. Our data revealed that after treatment with PR isoflavones, a dose-dependent inhibition of cell growth occurred in HS578T, MDA-MB-231, and MCF-7 cell lines. Results from cell cycle distribution and apoptosis assays revealed that PR isoflavones induced cell apoptosis through a caspase-3-dependent pathway and mediated cell cycle arrest in the G2/M phase. Furthermore, we observed that the serum metabolites of PR (daidzein sulfates/glucuronides) inhibited proliferation of the breast cancer cells at a 50% cell growth inhibition (GI(50)) concentration of 2.35 microM. These results indicate that the daidzein constituent of PR can be metabolized to daidzein sulfates or daidzein glucuronides that exhibit anticancer activities. The protein expression levels of the active forms of caspase-9 and Bax in breast cancer cells were significantly increased by treatment with PR metabolites. These metabolites also increased the protein expression levels of p53 and p21. We therefore suggest that PR may act as a chemopreventive and/or chemotherapeutic agent against breast cancer by reducing cell viability and inducing apoptosis.
Lin
Ying-Ju
YJ
Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.
Hou
Yu Chi
YC
Lin
Chia-Hung
CH
Hsu
Yu-An
YA
Sheu
Jim J C
JJ
Lai
Chih-Ho
CH
Chen
Bing-Hung
BH
Lee Chao
Pei-Dawn
PD
Wan
Lei
L
Tsai
Fuu-Jen
FJ
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019833:Genistein / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D029908:Pueraria / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D051028:bcl-2-Associated X Protein; C004742:daidzein; D019833:Genistein; D053453:Caspase 9; C033607:puerarin