Introduction of Geinstein/Soy
Genistein is a naturally occurring compound that belongs to the isoflavone class. It is described as a phytoestrogen and an angiogenesis inhibitor. It was isolated for the first time in 1899 from Genista tinctoria L. and named after the plant’s genus. Genista tinctoria; thus, the chemical name. Primary prevention through lifestyle interventions is a low-cost option for preventing a significant strain of chronic and degenerative diseases, like cancer, which is among the leading causes of morbidity and mortality worldwide.Epidemiologic and preclinical evidence in the last decade suggested that polyphenolic phytochemicals found in many plant foods have chemopreventive properties. As a result, there is an increase in interest in potential cancer chemopreventive agents derived from natural sources, such as polyphenols, representing a new, cost-effective approach to reducing the global cancer burden. Several epidemiologic studies found a link between a soy-rich diet and cancer prevention, attributed to the presence of genistein, a phenolic compound found in soy-based foods. Genistein acts as a chemotherapeutic agent against various types of cancer, primarily by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Genistein also exhibits synergistic behaviour with well-known anticancer drugs such as adriamycin, docetaxel, and tamoxifen, implying a potential role in combination therapy.Consumption of a lot of animal fat, energy, and alcohol raise the risk of cancer, whereas plant-based foods protect against cancer through various mechanisms of action due to the presence of phytochemicals.
The WHO’s International Agency for Research on Cancer reported that of the estimated 14.1 million adults worldwide diagnosed with cancer in 2012, 8.2 million died. Furthermore, based on recent trends in the incidence of significant cancers and projected population growth, more than 23 million new cancer cases per year are expected by 2030, which equates to 68 per cent more cancer cases than in 2012. . Lung, breast, and colorectal cancers are the most commonly diagnosed cancer types worldwide, while Lung, liver, and stomach cancers have a higher mortality rate. As a result, new, cost-effective approaches to reducing the world’s rising cancer burden are required. In addition, it is well understood that dietary habits have a significant impact on chronic diseases such as cancer. These biological and functional activities are attributed to plant foods’ micronutrient content, such as vitamins and minerals, and secondary plant metabolites, such as polyphenols, sulfur-containing compounds, Terpenes, and alkaloids. Polyphenols, which have been studied for their potential protective effects on human health, are the most studied of these compounds. These biological and functional activities are attributed to plant foods’ micronutrient content, such as vitamins and minerals, and plant secondary metabolites, such as polyphenols, sulfur-containing compounds, terpenes, and alkaloids. Polyphenols, which have been studied for their potential protective effects on human health, are the most studied of these compounds.
Isoflavones are plant-derived polyphenolic compounds with estrogenic (oestrogen agonist) and antiestrogenic (oestrogen antagonist) activity. They are the most abundant flavonoids in legumes, particularly soybeans, bound to sugars (glycosides). Genistein, daidzein, and glycitein are examples of soy isoflavones. The 3-phenylchromen-4-one backbone of these compounds, consisting of two benzene rings linked by a heterocyclic pyran ring, distinguishes them structurally. Genistein and its related isoflavones are polyphenols in addition to their heterocyclic core (contain several hydroxyl groups attached to core phenyl rings). The isoflavone genistein was initially labelled as a phytoestrogen due to its structural similarity to estrogens and low estrogenic activity. The flavone nucleus, composed of two benzene rings linked by a heterocyclic pyrene ring, is the primary structural feature of isoflavone compounds. Genistein has been shown to compete with 17-estradiol in ER binding assays due to its structural similarity., genistein has a 4 per cent binding affinity for ER- and an 87 per cent binding affinity for ER- compared to estradiol. Moreover, by interacting with the oestrogen receptor, genistein inhibits the binding of more potent estrogens simultaneously. It affects oestrogen metabolism, potentially playing a beneficial role in the prevention of hormone-related cancers. Following ingestion, genistein, like other isoflavones, is conjugated with glycoside and metabolized by intestine enzymes. In humans, genistein is thought to be metabolized to dihydrogenistein and 6′-hydroxy-O-desmethylangolensin. Plasma, prostatic fluid, breast aspirate and cyst fluid, urine, and faeces have all been found to contain genistein and its metabolites(Lamartiniere, 2000).
Soy Isoflavones in Cancer Therapy: Effects and Mechanisms
One of the most abundant and active flavonoids in soybeans is genistein. It has been discovered that it acts primarily by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis in estrogen-related malignancies such as PCa, Caspases, B cell lymphoma 2 (Bcl2)-associated X protein, Bcl-2, kinesin-like protein 20A, extracellular signal-regulated kinase 1/2, nuclear transcription factor B (NF-B), mitogen-activated protein kinase, an inhibitor of NF-B, and other proteins have been implicated in the molecular mechanisms of genistein’s anticancer and therapeutic effects2(Sarkar & Li, 2003).
GENISTEIN AND CANCER
Several epidemiologic studies have found a link between cancer prevention and a soy-rich diet. These studies arose from observations that in Asian countries with soy-rich diets, such as Japan and China,breast and prostate cancer incidence is lower than in the United States and Europe. Several meta-analyses suggest that eating soy foods reduces the risk of prostate cancer in men and is inversely related to the risk of breast cancer in Asian women but not found in Western Women. Furthermore, a recent meta-analysis discovered that soy isoflavone consumption could reduce the risk of breast cancer in both pre-and postmenopausal women in Asian countries3(Chen et al., 2014). Genistein is primarily present in its glycosylated form during the biogenesis process, usually in conjunction with a glucose molecule. Although genistein is consumed as a glycoside, a deglycosylation process occurs in the small intestine after ingestion. The body absorbs the free genistein aglycone in a variety of pharmacologic effects, including anticancer effects. Apart from genistein, synthetic derivatives, such as genistein glycosides, also show anticancer activity when tested in vitro. The anticancer activity of genistein glycosides varies depending on the sugar groups to which they are attached. The addition of acetylated sugar hydroxyls to genistein, for example, resulted in increased selectivity toward tumour cells 4(Spagnuolo et al., 2015). During the biogenesis process, genistein is found chiefly glycosylated with a glucose molecule. Although genistein is consumed as a glycoside, a deglycosylation process occurs in the small intestine after ingestion. The free genistein aglycone is absorbed by the body, resulting in various pharmacologic effects, including anticancer effects. Aside from genistein, synthetic derivatives such as genistein glycosides have been shown to have anticancer activity in vitro. The anticancer activity of genistein glycosides varies depending on the sugar groups to which they are attached. The addition of acetylated sugar hydroxyls to genistein, for example, resulted in increased selectivity toward tumour cells. It should be noted that the anticancer potency of genistein and its derivatives varies depending on their selectivity toward the target molecules in different types of cancer.
Breast cancer is one of the most common cancers in women, and triple-negative breast cancer (TNBC) has a significantly worse prognosis and a higher recurrence rate. The leading causes of the poor prognosis are an increased rate of metastasis and resistance to chemotherapy and radiotherapy. TNBC is characterized by a lack of all three genes encoding estrogen receptor (ER), progesterone receptor and Her2/neu, and often associated with BRCA1 mutation5. In Asian populations, soy consumption has been linked to a lower incidence of breast and prostate cancer. Asian people have a lower incidence of breast and prostate cancer. Asian people, owing to the presence of an isoflavone known as genistein. Hen genistein was compared to the other isoflavones; it was discovered to have structural similarities to 17-estradiol and weak estrogenic activity. It competes with 17-estradiol for the oestrogen receptor (ER),11 with a 4 per cent binding affinity for ER- and an 87 per cent binding affinity for ER-, playing a beneficial role in the treatment of hormone-related cancers6(Thiagarajan et al., 1998). A growing body of experimental evidence suggests that genistein inhibits human cancer cell growth by modulating genes involved in the cell cycle and apoptosis control. Genistein has been shown to inhibit the activation of the NF-B and Akt signalling pathways, both known to maintain a homeostatic balance between cell survival and apoptosis. Furthermore, genistein inhibits estrogen- and androgen-mediated signalling pathways during carcinogenesis. Taken together, in vivo and in vitro studies have demonstrated that genistein, one of the major soy isoflavones, is a promising cancer chemopreventive agent and that it may be helpful in the treatment of cancer. They are used as an adjuvant to cancer therapy due to their effects on reversing radioresistance and chemoresistance. Genistein is a known inhibitor of the protein-tyrosine kinase (PTK), which may slow cancer cell growth by inhibiting PTK-mediated signalling mechanisms7(Soy Isoflavones and Cancer Prevention: CLINICAL SCIENCE REVIEW: Cancer Investigation: Vol 21, No 5, n.d.).8. It has been discovered that soy isoflavones, including genistein, have antioxidant properties and protect cells from reactive oxygen species by scavenging free radicals, inhibiting the expression of stress response-related genes, thus reducing carcinogenesis. In vitro, genistein has been shown to inhibit the growth of both oestrogen and androgen receptor-positive and harmful breast and prostate cancer cells, as Well as estrogen-stimulated growth of breast cancer cells. Furthermore, we discovered that genistein is a potent inhibitor of the NF-B and Akt signalling pathways.
Soy consumption has been shown in human and animal studies to reduce the risk of colon cancer9. (Thiagarajan et al., 1998) According to epidemiological evidence, phytoestrogens may protect against the development of colorectal cancer. Numerous in vitro studies have demonstrated genistein’s anticancer properties against colorectal cancer and the mechanisms by which it exerts anticancer effects have been extensively researched. Genistein effectively suppresses colon cancer cell growth by inhibiting the PI3K/Akt pathway (143, 144), which plays an essential role in regulating colon cancer progression. Genistein influences ERs and tumour suppressor genes in colon cancer cells (145, 146). Furthermore, inhibiting the Wingless and integration 1 (Wnt) signalling pathway can prevent uncontrolled cell growth in a DLD-1 cell line10(Zhang & Chen, 2011).
Sources of Geinstein
Although genistein can be synthesized, humans get it through their diet. The conjugated form of genistein, known as genistein, is found in soy and soy products. As a result, when people consume soy and soy products, they are exposed to far more genistin than genistein. Following intestinal absorption, genistein undergoes first-pass metabolism in the liver as well as enterohepatic circulation. The byproducts of isoflavone metabolism can have a variety of effects on the body. Soy-based foods, such as soy cheese and soy drinks, are the best-known sources of genistein (i.e., soy milk and soy-based beverages). The genistein content of mature soybeans has been shown to range from 5.6 to 276 mg/100 g, with an average content of 81 mg/100 g frequently used for comparison. Although the total organic synthesis of genistein was accomplished in 1928, various other methods have also been obtained. A conventional microwave oven was used to perform the chemical synthesis of genistein by cyclizing the corresponding ketones. In addition to genistein, soy foods contain daidzein. This significant isoflavone differs from genistein in that it lacks the hydroxyl group at position 5. Both isoflavones can exist as aglycones or glycosides.
Legumes are the second most important source of genistein, containing 0.2 to 0.6 mg/100 g of the isoflavone alongside the other related isoflavone, daidzein 11(Liggins et al., 2021). The genus Lupinus (commonly known as lupin) is an example of a legume that is now widely cultivated for its seeds, which have a nutritional value comparable to soybean. Broad beans and chickpeas, which contain significant amounts of genistein but not as much as soybeans, are also essential legumes. The amount of genistein in fruits, nuts, and vegetables varies considerably; the estimated range is 0.03 to 0.2 mg/100 g.
The biotechnological approach of sprouting seeds to maximize isoflavonoid yield is the most common method to improve certain foods’ nutritional and medicinal values. As a result, the increased content of genistein and other isoflavonoid aglycones in germinated soybean seeds and related products has been well documented. Through genetic manipulation, genistein can also be obtained from nonlegume plant sources such as rice. Cloning the enzyme IFS from a genistein-rich soybean cultivar resulted in transgenic rice lines with a 30-fold increase in genistein content. Higher genistein content. Wdangerous medicinal value of genistein and amounted isoflavonoiaverage widely recognized, soy-based meat substitutes, soy milk, soy amount, gained popularity in Europe and the United States.
Although there is no clear evidence that consuming large amounts of isoflavones in the diet is harmful to humans, these compounds’ multiple and complex effects suggest that administering high doses of isoflavones could induce potentially dangerous effects. However, after a single amount that exceeded usual dietary intakes of purified unconjugated isoflavones, a single dose that exceeded average nutritional intakes of purified unconjugated isoflavones resulted in minimal clinical toxicity in healthy postmenopausal women. Anticancer agents’ genotoxicity, such as genistein, may be beneficial because it promotes cancer cell death by inducing apoptosis and other cytotoxic processes. However, these agents cause side effects consumption as a dietary supplement may cause Constipation, bloating, and nausea are common stomach and intestinal side effects. In some people and allergic reactions such as rash, itching, and anaphylaxis. It also affects phytoestrogens, and their active metabolites, such as equol, can persist in food/meat and influence consumers’ hormonal balance. Phytoestrogen consumption in animals may impact fertility, sexual development, and behaviour12(Sahin et al., 2019).
Several experimental and clinical studies suggest that genistein may have a therapeutic role in various types of cancer. The emergence of negative phenomena in cancer treatment, such as drug resistance, a high risk of relapse, and the unavailability or poor outcome of therapies such as surgery, chemotherapy, phototherapy, and radiotherapy, is well documented. As a result, there has been an increase in recent years. Focus on natural remedies that can improve the efficacy of chemotherapeutic treatment while also lowering adverse effects. Genistein can be included among these compounds because it exhibits synergistic behaviour when combined with well-known anticancer drugs such as adriamycin, docetaxel, and tamoxifen, implying a potential role in cancer treatment. Future research is needed to clarify the possible therapeutic and chemopreventive uses of genistein. It will be critical to look into the following in particular:
In experimental and clinical studies, the pharmacodynamics and pharmacokinetics of genistein and related compounds were investigated.
Possibilities for increasing genistein bioavailability.
The recommended therapeutic dose for the treatment of specific types of cancer.
Other molecular mechanisms that explain genistein’s anticancer effects (e.g., microRNAs)
Both experimental and clinical studies have revealed potential interactions between genistein and well-known anticancer drugs.
Chemotherapeutic agents and radiation cause oxidative stress and inflammation in cancer patients, resulting in side effects. Because of their multiple mechanisms of action, including antioxidant and anti-inflammatory effects, soy isoflavones may be used as dietary supplements to mitigate the adverse effects of anticancer drugs and radiation. Preclinical studies, meta-analyses, and clinical trials have all supported the use of soy isoflavones, particularly genistein, to prevent and control PCa. Still, more extensive placebo-controlled clinical trials are needed to investigate the potential use of genistein for alleviating the side effects of anticancer drugs and radiation therapy.