Genistein inhibits proliferation similarly in estrogen receptor-positive and negative human breast carcinoma cell lines characterized by P21WAF1/CIP1 induction, G2/M arrest, and apoptosis

Abstract

Genistein has been proposed to be responsible for lowering the rate of breast cancer in Asian women but the mechanism for this chemopreventive effect in vivo is unknown. In this study, we present in vitro evidence that genistein inhibits cell proliferation similarly in ER-positive and ER-negative human breast carcinoma cell lines. This inhibition is associated with specific G2/M arrest and induction of p21WAF1/CIP1 expression. Genistein results in a five-to six-fold increase in p21WAF1/CIP1 mRNA levels and a three- to four-fold increase in protein levels, only a 1.5-fold increase in p21WAF1/CIP1 transcription but a three- to six-fold increase in p21WAF1/CIP1 mRNA stability. The increase in p21WAF1/CIP1 is followed by increased apoptosis. The similar effects of genistein on a number of breast carcinoma cell lines with different ER and p53 status suggest that the actions of genistein reported here are mediated through ER and p53 independent mechanisms. The chemopreventive effects of genistein in vivo could be mediated along an identical or similar anti-proliferative pathway.

Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells

“…S1), 3 respectively, and are comparable with reported IC 50 values in this cell line (9, 11 -13 concentrations did not change cell viability after 48 h (data not shown), in agreement with other reports (2,14,19). Cells in passages 10 to 16 growing in the presence of phytochemicals or DMSO, as control, were used for analyses.…”

“…The number of cells from each treatment was estimated as a percentage of the number in the DMSO control. The number of cell generations (g) was counted according to the formula g = ln 2 (N/N 0 ), where N is the final number of cells. The time of growth comprises the sum of the time for initial adhesion (considered here to be 5 h), the time of complete division cycles (p  g), and a part of the unfinished last cycle (=p/2 on average), where p is one cell cycle duration.…”

“…Therefore, many reported effects obtained in cell culture studies may be irrelevant for in vivo activity. All the chemopreventive phytochemicals induce cell cycle arrest and apoptosis in a variety of cancer cells, albeit often at nonphysiologic doses (2,3). Therefore, we investigated whether any positive antitumorigenic effects (e.g., growth, apoptosis, and expression of selected biomarkers) could be detected following extended treatments with low doses.…”

Inhibition of mitochondrial proton F0F1‐ATPase/ATP synthase by polyphenolic phytochemicals

“…However, several earlier studies indicated that the tyrosine kinase was not required for the inhibitory eect of genistein on tumour growth (Barnes & Peterson, 1995;Stevens et al, 1994;Shao et al, 1998), nor for biochanin A and daidzein. Other mechanisms have been Figure 5 Eects of resveratrol, genistein and quercetin on porcine cerebral cortex Na + /K + -ATPase.…”

Differentiated impact of procyanidins from evening primrose on human breast cancer cells

“…In 2008, over 12 million new cancer cases were diagnosed worldwide, breast cancer being one of the most frequently diagnosed in women, and the one characterized with the highest mortality rate [10]. However, a large body of data exists on the influence of polyphenols of plant origin on breast cancer [11][12][13][14]. For instance, an extract from the fruit of Terminalia chebula Retz.…”