Chemopreventive Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
In terms of possible cancer chemopreventive properties, genistein has been shown to act as an angiogenesis inhibitor, and its ability to inhibit key proteins that control cell division and cell survival such as the kinases may contribute. In this context, in vitro studies have suggested that moderate doses of genistein have inhibitory effects on prostate, cervix, brain, breast, and colon cancer cells. It has been suggested that this activity may be due to the ability of genistein to inhibit tyrosine kinases known to be important in proliferation signal cascades, and/or through inhibiting DNA topoisomerase II. Also, in some hormone-sensitive tumor cell types, genistein may compete with 17β-estradiol (estrogen) at estrogen receptors due to its structural similarity.
Role of Antioxidant-Based Nutraceuticals in Translational Medicine: Review
Megh R. Goyal, Durgesh Nandini Chauhan in Assessment of Medicinal Plants for Human Health, 2020
Genistein is an isoflavone that is abundantly found in soybeans and in most products containing soy protein. Genistein is a negative regulator of signaling molecules that are involved in control of cell cycle. And it also helps in regulation of apoptosis mechanism of cancer cells. It induces growth inhibition and apoptotic cell death in androgen unresponsive prostate cancer cells by inhibiting Akt/FOXO3a/GSK-3β/AR and Akt/mTOR signaling networks through suppression of tyrosine kinase activity.2 Genistein has structural similarity to estradiol and can bind to estrogen receptors, α and β. It can inhibit cell growth and proliferation of breast and prostate cancer cells.21,34 Additionally, it also displays antioxidant and anticarcinogenic effects through inhibition of NFĸB activation.3,17 Other important targets of genistein include Akt kinase, Wnt/β-catenin, and Notch signaling.1,21,44 In addition to these carcinogenic pathways, genistein also directly regulates expression of several other genes that are involved in DNA damage repair, such as GPx, GADD45, glutathione reductase, and GST1, thereby offering protection against oxidative stress and carcinogenesis.21
Nutraceutical’s Role in Proliferation and Prevention of Prostate Cancer
Sheeba Varghese Gupta, Yashwant V. Pathak in Advances in Nutraceutical Applications in Cancer, 2019
Genistein has structural similarity to estradiol and has weak estrogenic properties due to its ability to bind to estrogen receptors [77,79]. Genistein antiprostatic effects are mediated by various cell signaling pathways [80]. Genistein suppresses vascular endothelial growth factor (VEGF), thereby inhibiting angiogenesis in prostate cancer [81]. In human prostate cell lines, genistein was shown to inhibit p38 mitogen-activated protein kinase (MAPK) and matrix metalloproteinase type 2 (MMP-2) in the nanomolar range, which corresponds to its dietary intake, blood concentrations [82]. In androgen-independent prostate cancer PC3 and DU145 cell lines microRNA-151 (miR-151) are upregulated [83]. It was demonstrated that genistein inhibits oncogenic miR-151 in both PC3 and DU145 cell lines [83]. It was also demonstrated that genistein treatment with radiation in PC-3 prostate cancer cells promotes apoptosis and arrests G2/M cell cycle by inhibiting radiation-induced NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation [84]. It is evident that genistein has antimetastatic effect and also modulates the metastatic potential markers [85].
Role of Plant-Derived Flavonoids in Cancer Treatment
Published in Nutrition and Cancer, 2023
Prabha Tiwari, Kaushala Prasad Mishra
Genistein, a phytoestrogen, an angiogenesis and RTKs inhibitor, is the most studied isoflavone (130). Genistein can antagonize estrogen-and androgen-mediated signaling pathways in the process of carcinogenesis (131). Genistein modulates cell cycle arrest through regulation of ATM, Chk1, Chk2, Cdk1/cyclin B and Cdk inhibitor p21Waf1/Cip1 (132). Recent studies have hypothesized that genistein functions as a direct PLK1 kinase inhibitor, a master mitotic kinase (133,134). Furthermore, genistein can inhibit cancer growth and angiogenesis through regulation of various cellular targets and signaling pathways such as Akt/PKB, bFGF, COX-2, ERK, HIF, IGF, JNK, MAPK, PDGF, NF-κB, uPA and VEGF (130). Moreover, studies have suggested that genistein can modulate epigenetic events such as DNA methylation and chromatin modifications in cancer prevention and therapy (135).
Fermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells
Published in Nutrition and Cancer, 2022
Xinshou Ouyang, Yonglin Chen, Boodapati S. Tejaswi, Suyavaran Arumugam, Eric Secor, Theresa R. Weiss, Michael Leapman, Ather Ali
Genistein is an isoflavone that is found in a number of plants with fava beans and soybeans being major food sources. Genistein has been reported to have a very wide range of biological properties including being an antioxidant, stimulating autophagy, activation of Nrf2, and inhibition of a number of receptors including glycine and nicotinic receptors (19–21). Genistein has been shown to reduce tumor cell proliferation and induce tumor cell apoptosis, making it relevant to ask if the effects of Q-CAN PLUS in Figure 1 were due to its genistein content (22). The genistein composition of Q-CAN PLUS was quantified as detailed in Materials and Methods and was 0.055%. An IC50 of Q-CAN PLUS in the range of 3.8–9 mg/ml therefore corresponds to a genistein concentration of 0.038 and 0.09 mg/ml. We therefore performed a dose–response curve of genistein with the same cell lines and under the same conditions as for Q-CAN PLUS. As Figure 2 shows, this resulted in a dose–response curve demonstrating the ability of genistein to inhibit viability of the same four cancer cell lines. The IC50 of genistein for each of the cell lines was significantly greater than for Q-CAN PLUS (Figure 1). Taking into consideration the IC50 of genistein and the concentration of genistein in Q-CAN PLUS, it is clear that the genistein content of Q-CAN PLUS is not responsible for the majority reduction in tumor cell viability seen in Figure 1. Genistein may however be a contributing component to it.
Genistein affects gonadotrophin-releasing hormone secretion in GT1-7 cells via modulating kisspeptin receptor and key regulators
Published in Systems Biology in Reproductive Medicine, 2022
Jingyuan Xiong, Ye Tian, Aru Ling, Zhenmi Liu, Li Zhao, Guo Cheng
Genistein, an important member of soy isoflavones, is a naturally occurring phytoestrogen displaying structural and functional similarities with 17β-estradiol, directly impacting the endocrine and reproductive systems (Křížová et al. 2019). Dietary genistein is considered to be a critical factor in advancing puberty and reproductive maturation for children and adolescents (Marks et al. 2017; Ali et al. 2020). In adults, supplements of isoflavones were reported to reduce menopausal symptoms, and lower the risk of breast and prostate cancer (Lethaby et al. 2007; Shu et al. 2009; Lund et al. 2011). On the contrary, case reports on a few women of reproductive age indicated that intake of phytoestrogens might exert adverse effects, including dysmenorrhea and endometriosis (Chandrareddy et al. 2008). Although numerous pieces of evidence suggested that genistein could affect endocrine and reproductive functions, the detailed cell and molecular effects and mechanisms remain to be clarified.
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