Beneficial effects of genistein in suppression of proliferation, inhibition of metastasis, and induction of apoptosis in PC3 prostate cancer cells

Shafiee, Gholamreza; Saidijam, Massoud; Tayebinia, Heidar; Khodadadi, Iraj

doi:10.1080/13813455.2020.1717541

Cited by 34 publications

(25 citation statements)

References 31 publications

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“…Genistein. Genistein suppressed the metastatic potential of PC-3 prostate cancer cells through the reduction of MMP-2 activity [ 97 ]. Its anti-metastatic potential in SW480 colorectal cancer cells was mediated possibly through inhibition of TTTY18/Akt pathway [ 98 ].…”

Section: Targeting Metastatic Cancermentioning

confidence: 99%

Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

127

135

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Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.

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Section: Targeting Metastatic Cancermentioning

confidence: 99%

Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

127

135

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“…Our prior studies and studies by others have determined that GCP and genistein can mediate apoptosis via AR-independent mechanisms. For example, Shafiee et al have demonstrated that genistein can promote apoptosis in PC3 cells, a cell line which lacks AR [43], and our group demonstrated that GCP mediates apoptosis via inhibition of mTOR14. Grossebrummel et al found that genistein can mediate increased apoptosis of cancer cells via increasing expression levels of caspase 3, 7, and 12, as well as by causing increased cellular stress [44].…”

Section: Discussionmentioning

confidence: 73%

Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells

et al. 2020

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Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (p < 0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3βHSD (p < 0.001), 17βHSD (p < 0.001), CYP17A (p < 0.01), SRB1 (p < 0.0001), and StAR (p < 0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (p < 0.001). Genistein caused similar decreases in the expression of 17βHSD and CYP17A (2.5-fold (p < 0.001) and 1.5-fold decrease (p < 0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3βHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted.

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“…Genistein has displayed anticancer effects against breast, colon, lung, thyroid, gastric, and prostate cancers by modulating a variety of molecular targets, such as apoptotic markers caspases, Bcl and Bax, nuclear factor-κB, an inhibitor of NF-κB, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/Akt (PI3K/Akt), extracellular signal-regulated kinase 1/2 (ERK 1/2), and Wingless and integration 1/β-catenin (Wnt/ß-catenin) signaling pathway ( Tuli et al, 2019 ). It can show pro-apoptotic, anti-proliferative, and anti-metastatic activities in vitro on PC3 prostate cancer cells through triggering apoptosis by activating caspase-3 related pathways, by reducing cell survival via inhibition of p38MAPK at both gene expression and protein levels, and by inhibiting metastasis through the blockage of MMP2 activity ( Shafiee et al, 2020 ). Genistein is documented as clinically safe and effective when combined with standard fluoropyrimidine and platinum-based drug, oxaliplatin, with or without Bevacizumab, in the treatment of metastatic colon cancer ( Pintova et al, 2019 ).…”

Section: Potential Microalgal Antioxidants For Use In Cancer Therapiementioning

confidence: 99%

Medicinal Prospects of Antioxidants From Algal Sources in Cancer Therapy

Ferdous

Yusof

2021

Front. Pharmacol.

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Though cancer therapeutics can successfully eradicate cancerous cells, the effectiveness of these medications is mostly restricted to several deleterious side effects. Therefore, to alleviate these side effects, antioxidant supplementation is often warranted, reducing reactive species levels and mitigating persistent oxidative damage. Thus, it can impede the growth of cancer cells while protecting the normal cells simultaneously. Moreover, antioxidant supplementation alone or in combination with chemotherapeutics hinders further tumor development, prevents chemoresistance by improving the response to chemotherapy drugs, and enhances cancer patients’ quality of life by alleviating side effects. Preclinical and clinical studies have been revealed the efficacy of using phytochemical and dietary antioxidants from different sources in treating chemo and radiation therapy-induced toxicities and enhancing treatment effectiveness. In this context, algae, both micro and macro, can be considered as alternative natural sources of antioxidants. Algae possess antioxidants from diverse groups, which can be exploited in the pharmaceutical industry. Despite having nutritional benefits, investigation and utilization of algal antioxidants are still in their infancy. This review article summarizes the prospective anticancer effect of twenty-three antioxidants from microalgae and their potential mechanism of action in cancer cells, as well as usage in cancer therapy. In addition, antioxidants from seaweeds, especially from edible species, are outlined, as well.

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Beneficial effects of genistein in suppression of proliferation, inhibition of metastasis, and induction of apoptosis in PC3 prostate cancer cells

Cited by 34 publications

References 31 publications

Flavonoids in Cancer Metastasis

Flavonoids in Cancer Metastasis

Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells

Medicinal Prospects of Antioxidants From Algal Sources in Cancer Therapy

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