Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling

Abstract

Abstract. Genistein is a soybean isoflavone; in its aglycone it has various biological activities. Animal experiments, clinical studies and epidemiological investigations suggest that genistein has preventative and curative functions for a number of diseases, particularly in cancer. The present study explored the potential anti-cancer effect of genistein by observing its role in inhibiting A549 human lung cancer cell proliferation and investigating the possible mechanism. A549 cells were exposed to various concentrations of genistein (0, 10, 25, 50, 100 and 200 µM; dissolved in physiological saline) for 1, 2 and 3 days. Subsequently, the viability of A549 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined using a flow cytometer, caspase 3/9 activity was measured using commercial kits, reverse transcription quantitative polymerase chain reaction was used to analyze the miR-27a expression and western blotting was used to investigate MET protein expression. The results suggested a significant inhibition of A549 cell growth following treatment with genistein in a time-and dose-dependent manner. The current study also indicated that treatment with genistein significantly induces cell apoptosis and promotes caspase-3/9 activation of A549 cells in a dose-dependent manner. Further functional assays revealed that the anti-cancer effect of genistein activated microRNA-27a (miR-27a) expression levels and reduced MET protein expression in A549 cells. In conclusion, the present study demonstrates that genistein inhibits A549 human lung cancer cell proliferation. Furthermore, this study reports, for the first time, a correlation between the anti-cancer effect of genistein and miR-27a-mediated MET signaling.

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

“…As A549 line has been widely used as a model system to study human alveolar carcinoma, cytotoxic profile of flavonoids in these cells was previously characterized with the results very similar to those measured in our work. Indeed, the IC 50 value of 72.2 µM for quercetin is close to the inhibitory constants published by Loizzo et al (26), Tan et al (27)(28)(29), Robaszkiewicz et al (30), and Chan et al (31); and IC 50 values more than 100 µM were previously reported for fisetin (32), hesperetin (33-35), luteolin (32,36), chrysin (35), baicalein (34), daidzein (37), and genistein (38). Based on our results presented in this article, cytotoxic activity profiles of flavonoids were rather similar for both A549 and HCC-44 lung cancer lines, despite the gender difference of initial origin of these cells.…”

miR-27a Downregulation Promotes Cutaneous Squamous Cell Carcinoma Progression via Targeting EGFR

“…Further, low expressed miR-27a was related to high grade in colorectal cancer (18). miR-27a inhibited A549 cell proliferation via MET signaling (19) and in esophageal squamous cell carcinoma functioned as a tumor suppressor through binding to oncogene KRAS (20). Consistent with these studies, we found declined levels of miR-27a in cSCC and exogenous miR-27a suppresses cell proliferation and leads to the metastasis inhibition of cSCC significantly in vivo and in vitro.…”

MicroRNA-Mediated Health-Promoting Effects of Phytochemicals

“…A few studies suggested that phytochemicals can bind to miRNAs directly or affect the transcription or processing of miRNAs by regulating a third molecule [12,13,14]. Interestingly, genistein regulates specific microRNAs, such as miR-27a and miR-1260b, in various cancer cells to elicit anticancer functions [58,59,60,61,62,63]. A distinct mechanism likely exists to regulate specific microRNA expression.…”

“…Genistein is a major isoflavonoid isolated from soybeans [57]. Genistein has been shown to prevent multiple cancers by regulating the expression of specific oncogenic miRNAs, such as miR-27a and miR-1260b [58,59,60,61,62,63]. Genistein downregulates miR-27a expression in uveal melanoma, ovarian cancer, pancreatic cancer, and lung cancer cells to inhibit cell proliferation, migration, or invasion [60,61,62,63].…”

“…Genistein has been shown to prevent multiple cancers by regulating the expression of specific oncogenic miRNAs, such as miR-27a and miR-1260b [58,59,60,61,62,63]. Genistein downregulates miR-27a expression in uveal melanoma, ovarian cancer, pancreatic cancer, and lung cancer cells to inhibit cell proliferation, migration, or invasion [60,61,62,63]. Zinc finger and BTB domain (Broad-Complex, Tramtrack and Bric a brac) containing 10 and Sprouty2 were validated as targets of miR-27a in uveal melanoma cells and ovarian cancer cells, respectively [60,62].…”