Apoptosis of human primary gastric carcinoma cells induced by genistein

Abstract

AIM:To investigate the apoptosis in primary gastric cancer cells induced by genistein, and the relationship between this apoptosis and expression of bcl-2 and bax. METHODS:MTT assay was used to determine the cell growth inhibitory rate in vitro. Transmission electron microscope and TUNEL staining were used to quantitatively and qualitatively detect the apoptosis of primary gastric cancer cells before and after genistein treatment. Immunohistochemical staining and RT-PCR were used to detect the expression of apoptosisassociated genes bcl-2 and bax. RESULTS:Genistein inhibited the growth of primary gastric cancer cells in dose-and time-dependent manner. Genistein induced primary gastric cancer cells to undergo apoptosis with typically apoptotic characteristics. TUNEL assay showed that after the treatment of primary gastric cancer cells with genistein for 24 to 96 h, the apoptotic rates of primary gastric cancer cells increased time-dependently. Immunohistochemical staining showed that after the treatment of primary gastric cancer cells with genistein for 24 to 96 h, the positivity rates of Bcl-2 proteins were apparently reduced with time and the positivity rates of Bax proteins were apparently increased with time. After exposed to genistein at 20 µmol/L for 24, 48, 72 and 96 respectively, the density of bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time.

Genistein and Cancer: Current Status, Challenges, and Future Directions

“…In preclinical models, genistein was able to induce apoptosis in primary gastric cancer cells (20 mM for 24-72 h) by downregulating the expression of the antiapoptotic protein B cell lymphoma 2 (Bcl-2) and upregulating the expression of proapoptotic Bcl-2-associated X protein (Bax) (117). A similar modification of the Bcl-2:Bax ratio was considered responsible for the ability of genistein (0.5, 1, and 1.5 mg/kg) to induce apoptosis in SG7901 cells transplanted into subcutaneous tissue of nude mice (118).…”

Isoflavones from Phytoestrogens and Gastric Cancer Risk: A Nested Case-Control Study within the Korean Multicenter Cancer Cohort

“…Isoflavones, such as genistein and daidzein, directly affect gastric cancer cells (11,22,23). Genistein could participate in apoptosis by downregulation of apoptosis-regulated gene Bcl2 and upregulation of apoptosis-regulated gene Bax (38,39). Additionally, genistein could inhibit gastric cancer cell growth and proliferation by cell cycle arrest at G 2 and early M phase and angiogenesis and induce cell apoptosis (11,22); daidzein could inhibit gastric cancer cell growth by cell cycle arrest at G 1 phase (22).…”

Antioxidant Function of Isoflavone and 3,3′-Diindolylmethane: Are They Important for Cancer Prevention and Therapy?

“…The results from our laboratory and other investigators showed that isoflavone inhibited the growth of various cancer cells, including leukemia, lymphoma, neuroblastoma, breast, prostate, lung, gastric, ovarian, and head and neck cancer cells (1,21,29,32,45,70,78,81,127). The inhibition of cancer growth by isoflavone could be mediated by the induction of apoptosis and the modulation of expression of the genes related to the cell growth and apoptotic processes (1,70,78,81,128).…”

“…The isoflavone genistein also inhibited constitutive and inducible NF-jB activation and decreased IL-8 production in human cystic fibrosis bronchial gland cells (115). It is also reported that isoflavone inhibited NF-jB activation in various solid cancers, including neuroblastoma, breast, prostate, lung, gastric, ovarian, and head and neck cancer cells (1,32,45,78,81,127), suggesting that downregulation of NF-jB signaling is an important mechanism by which isoflavone functions as an antioxidant, and thereby inhibits cancer development and progression (Fig. 4).…”