Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells

Wang, Shulhn Der; Chen, Bor Chyuan; Kao, Shung Te; Liu, Ching Ju; Yeh, Chun-Chieh

doi:10.1186/1472-6882-14-26

Cited by 49 publications

(30 citation statements)

References 44 publications

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“…Our study revealed that genistein and daidzein increased the ovarian follicular reserve in middle-aged rats by stepping down the transition from primordial to primary follicle and by depressing follicular atresia. The mechanisms may be explained by the suppression of cellular proliferation through the inhibition of key steps in the signal transduction pathways [46] and cell cycle progression [47,48], indicating that genistein and daidzein may play a role in suppressing the process of follicular development by scavenging and suppressing intracellular reactive oxygen intermediates. Therefore, we presume that phytoestrogens may protect follicles from atresia due to the decrease of oxidative stress in the ovary.…”

Section: Discussionmentioning

confidence: 98%

Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female rats

et al. 2015

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The aim of this study was to assess the effects of genistein (G) and daidzein (D) on the histological, hormonal, and functional parameters of the pituitary-ovarian axis in middle-aged female rats, and to compare these effects with the effects of estradiol (E), commonly used in the prevention and treatment of menopausal symptoms. Middle-aged (12 month old) Wistar female rats subcutaneously received 35 mg/kg of G, or 35 mg/kg of D, or 0.625 mg/kg of E every day for 4 weeks. Each of the treated groups had a corresponding control group. An intact control group was also established. G and D did not change the intracellular protein content within gonadotropic and lactotropic cells, but vacuolization was observed in all the cell types. In contrast, E caused an inhibition of gonadotropic and stimulation of lactotropic cells. Also, ovaries of middle-aged female rats exposed to G or D have more healthy primordial and primary follicles and less atretic follicles. E treatment in the ovaries had a mostly negative effect, which is reflected by the increased number of atretic follicles in all tested classes. G and D provoked decrease in CuZnSOD and CAT activity, while E treatment increased MnSOD and decreased CuZnSOD and GSHPx activity. All the treatments increased serum estradiol and decreased testosterone levels, while D and E increased the serum progesterone level. In conclusion, soy phytoestrogens exhibited beneficial effects on pituitary-ovarian function in middle-aged female rats, as compared to estradiol.

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Section: Discussionmentioning

confidence: 98%

Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female rats

et al. 2015

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“…In fact, genistein has been shown to inhibit the migration of 3 cell lines (HepG2, SMMC-7721, and Bel-7402 cells) (109). Moreover, it promotes anti-invasive and antimetastatic effects against 12-O-tetradecanoylphorbol-13-acetate-mediated metastasis via downregulation of matrix metalloproteinase 9 (MMP-9) and epidermal growth factor receptor (EGFR) and subsequent suppression of NF-kB and activator protein 1 (AP-1) transcription factors through inhibition of MAPK, inhibitor of NF-kB (IkB), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways (110).…”

Section: Genistein and Cancermentioning

confidence: 99%

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

Spagnuolo

Russo

Orhan

et al. 2015

Advances in Nutrition

436

259

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Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.

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“…Thus, inhibition of NF-κB activity in cancer/endothelial cells may provide a target for cancer treatment and/or prevention. Recently, Wang et al [109] have found that genistein suppressed MMP-9 transcription by inhibiting NF-κB activity. It suppressed 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced NF-κB—specific DNA-protein binding compared to TPA via inhibition of NF-κB nuclear translocation through inhibitor of kappa B inhibitory signaling pathways.…”

Section: Antiangiogenic Effect Of Soy Isoflavonoidsmentioning

confidence: 99%

Soy and Breast Cancer: Focus on Angiogenesis

Varinská

Gál

Mojžišová

et al. 2015

IJMS

153

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Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

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Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells

Cited by 49 publications

References 44 publications

Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female rats

Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female rats

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

Soy and Breast Cancer: Focus on Angiogenesis

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