Resveratrol and Its Influence on Cancer Prevention

Worldwide, cancer continues to pose a serious threat to public health, calling for constant study and investigation of viable remedies. Resveratrol has emerged as one of the chemicals being investigated for its potential to combat cancer. Apples and grapes are only two examples of the many fruits and vegetables that naturally contain resveratrol, a polyphenolic stilbene. Numerous studies have demonstrated the many health advantages of resveratrol, which include its anti-inflammatory, antioxidant, cardio-protective, and anti-cancer qualities. Resveratrol is a promising new therapy and preventative option for cancer as research in the lab and on animals have shown that it affects cancer cells in a variety of ways. To evaluate resveratrol's effectiveness in managing cancer, we also look at how it affects molecular pathways in cancer and analyze data from pre-clinical and clinical studies.

Cancer

The word "cancer" refers to a broad category of intricate illnesses marked by the body's aberrant cells proliferating and spreading out of control. These aberrant cells can spread to other areas of the body and infiltrate nearby tissues, where they can grow into masses or tumors. Any organ or tissue can develop cancer, which is caused by a confluence of risk factors such as exposure to carcinogens, genetic mutations, and other abnormalities.

Types of Cancer

Cancer encompasses numerous distinct types, classified according to the location of the primary tumor and the specific cell types involved. Some prevalent types of cancer include:

·       Breast Cancer

·       Lung Cancer

·       Prostate Cancer

·       Colorectal Cancer

·       Skin Cancer (Melanoma)

·       Leukemia

·       Lymphoma

·       Pancreatic Cancer

·       Ovarian Cancer

·       Bladder Cancer

Mechanism of Cancer

Complex cellular and molecular pathways control the onset and spread of cancer. Cell division and proliferation are strictly controlled processes in a healthy organism, guaranteeing that damaged or old cells are replaced with new, healthy ones. But cancer throws this balance off. The following are the main mechanisms behind cancer:

·       Genetic Mutations: One of the main causes of cancer is a genetic mutation. Uncontrolled cell growth and division can be caused by mutations in certain genes.

·       Tumor Formation: A tumor is the result of an aberrant cell aggregation and can be malignant (cancerous) or benign (non-cancerous).

·       Metastasis: Cancerous tumors can spread to other parts of the body by invading surrounding tissues and gaining access to the blood or lymphatic system.

·       Angiogenesis: To obtain the nutrients and oxygen required for tumor development, cancer cells have the ability to induce the formation of new blood vessels.

Resveratrol

Natural polyphenol resveratrol is present in red wine, grapes, and other plant sources. It has drawn a lot of interest because it may help obese people lose weight and control their Type 2 Diabetes Mellitus (T2DM). We shall examine resveratrol's physiological function, advantages, and effects on obesity and type 2 diabetes in this post. We will also go over the results of pre-clinical and clinical studies that provide insight into resveratrol's potential as a treatment for certain ailments.

A stilbenoid is a polyphenolic molecule that includes resveratrol. Plants naturally produce it in response to a variety of stresses, including damage, fungal infections, and UV radiation exposure. Due to its correlation with red wine and the "French Paradox," which describes the low risk of heart disease among French people while eating a diet high in saturated fats, resveratrol has gained significant interest. Resveratrol helps plants become more resilient overall by acting as a shield against environmental stresses. Resveratrol has anti-ageing, anti-inflammatory, and antioxidant effects in animals. Its capacity to activate sirtuins, a family of proteins essential for controlling a number of cellular functions, is thought to be the cause of these effects [1].

Benefits

Numerous health advantages of resveratrol have been studied scientifically, including:

·       Antioxidant Properties: Resveratrol functions as an antioxidant to shield cells from free radical-induced oxidative damage. Its capacity to prevent different illnesses and have anti-ageing benefits may be attributed to this feature.

·       Anti-Inflammatory Effects: Research has shown that resveratrol has anti-inflammatory qualities, which lower inflammation and the chance of chronic illnesses linked to it.

·       Cardiovascular Health: By encouraging blood vessel dilatation, lowering blood pressure, and preventing blood clot formation, resveratrol may contribute to improved cardiovascular health.

·       Neuroprotective Effects: Research indicates that resveratrol may shield nerve cells from harm, which may help with diseases such as Alzheimer's [2].

Role of Resveratrol in Cancer

Natural polyphenol molecule resveratrol is present in many plant sources and has drawn a lot of attention due to its potential use in cancer treatment and prevention. Its well-known anti-inflammatory and antioxidant qualities are thought to help prevent cancer by reducing oxidative stress, which is strongly associated with the growth of cancer.

Resveratrol inhibits oncogenic KRAS expression, which impedes the growth and creation of tumors and has an influence on colorectal cancer. By downregulating hexokinase II via the epidermal growth factor receptor (EGFR)/Akt/ERK1/2 pathway, it inhibits glycolysis in non-small cell lung cancer (NSCLC) and prevents carcinogenesis and progression. Resveratrol has pro-apoptotic and anti-proliferative effects in human prostate cancer cells (LNCaP) via inducing cyclooxygenase-2 (COX-2) production, activating ERK1/2, and enhancing p53-dependent anti-proliferation gene expression [3].

Resveratrol inhibits the adhesion of ovarian cancer cells to the peritoneal mesothelium by upregulating the production of soluble hyaluronic acid and downregulating α5β1 integrins. It suppresses the development of HeLa cells by downregulating Phospholipid Scramblase 1 (PLSCR1). Resveratrol causes apoptosis and growth suppression in HepG2 cells via inducing p53 expression, activating caspase-3 and caspase-9, and changing the Bax/Bcl-2 ratio.

Additionally, by inhibiting the epithelial-to-mesenchymal transition that is facilitated by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), resveratrol hinders the invasion and migration of human gastric cancer cells. By blocking STAT3, it prevents breast cancer from spreading by preventing the generation of transforming growth factor β (TGF-β) and tumor-evoked regulatory B cells (tBregs). But depending on the dose, resveratrol's effects on breast cancer might differ. While low doses may promote ERα+ cell proliferation by altering estrogen levels, high amounts inhibit estrogen receptor alpha positive (ERα+) breast cancer [3].

How Resveratrol Treats Cancer

Research into the specific mechanisms through which resveratrol treats cancer is ongoing. Nonetheless, several potential pathways and mechanisms have been identified:

·       Apoptosis Induction: Resveratrol is shown to promote apoptosis, a programmed cell death process that helps eliminate cancerous cells.

·       Anti-Inflammatory Effects: Chronic inflammation is a cancer risk factor, and resveratrol's anti-inflammatory properties can mitigate this risk.

·       Inhibition of Angiogenesis: Resveratrol may hinder the formation of new blood vessels in tumors, restricting their nutrient supply and growth.

·       Cell Cycle Regulation: Resveratrol can modulate the cell cycle, preventing uncontrolled cell division [4].

·       DNA Repair Enhancement: Some studies suggest that resveratrol can enhance DNA repair mechanisms, reducing the risk of mutations leading to cancer.

·       Increased Sensitivity to Chemotherapy: Resveratrol can enhance the sensitivity of certain cancer cells to chemotherapy agents, potentially overcoming chemoresistance mechanisms.

·       Reduction of Chemotherapy Side Effects: By boosting antioxidant and anti-inflammatory activities, resveratrol may mitigate chemotherapy side effects like anorexia, fatigue, depression, neuropathic pain, and cognitive impairment [5].

It is essential to acknowledge that while resveratrol shows promise in these areas, more research is required to establish the optimal dosages and administration methods, as well as to determine its efficacy in clinical settings.

How Resveratrol Targets Molecular Pathways in Cancer

Researchers have identified various molecular pathways that resveratrol may affect in the context of cancer:

·       PI3K/AKT Pathway: Resveratrol has demonstrated the ability to inhibit this pathway, which plays a role in cell survival and proliferation. Inhibition of PI3K/AKT can curtail cancer cell growth.

·       NF-κB Pathway: Resveratrol can suppress NF-κB, a transcription factor associated with inflammation and cell survival. Inhibiting NF-κB can reduce cancer cell viability.

·       Wnt/β-catenin Pathway: Resveratrol may modulate this pathway, which is linked to cell proliferation and cancer. Targeting Wnt/β-catenin may help control cancer growth [6].

Pre-clinical and Clinical Trials of Resveratrol in Cancer

Pre-clinical and clinical trials play an integral role in evaluating the potential of resveratrol in cancer prevention and treatment.

Pre-clinical Studies

Numerous laboratory and animal studies have provided promising evidence of resveratrol's anti-cancer effects, which include its ability to:

·       Suppress Tumor Growth: Resveratrol has demonstrated the potential to inhibit tumor growth in various cancer types, such as colorectal cancer, breast cancer, and prostate cancer.

·       Induce Apoptosis: Resveratrol has been shown to induce apoptosis in cancer cells, contributing to their elimination [7].

·       Inhibit Angiogenesis: Resveratrol's ability to inhibit angiogenesis can hinder the development of new blood vessels crucial for tumor growth and metastasis.

·       Modulate Signaling Pathways: Resveratrol has been found to modulate signaling pathways involved in cell death, including apoptosis, autophagy, mitotic catastrophe, and senescence.

·       Enhance Chemotherapy and Radiotherapy: Resveratrol's capacity to augment the effectiveness of chemotherapy and radiotherapy holds promise for combination therapies.

·       Prevent Cancer: Preclinical studies have demonstrated resveratrol's potential to prevent the development of cancer, which is particularly noteworthy in colorectal cancer, breast cancer, and prostate cancer [8].

Clinical Trials

Clinical trials involving human participants are essential to determine the safety and efficacy of resveratrol in cancer prevention and treatment. Several key findings from these trials include:

·       Prostate Cancer: A clinical trial showed that resveratrol could delay cancer recurrence in prostate cancer patients, a significant finding given the high recurrence rate in this type of cancer.

·       Colorectal Cancer (CRC): Clinical trials in CRC patients have evaluated the physiological impacts of resveratrol. Some results suggest that resveratrol could be a promising agent for CRC prevention and treatment when used in combination with radiotherapy or chemotherapy [9].

·       Liver Cancer: While preclinical studies have shown effectiveness in treating liver cancer, ongoing clinical trials aim to assess resveratrol's potential in human patients.

·       Breast Cancer: The effects of resveratrol on breast cancer cells are subject to ongoing research, with some studies showing its anticancer properties while others suggest caution due to potential estrogenic effects.

·       Resveratrol has been researched as a combination drug for cancer treatment. One study with patients with biochemically recurring prostate cancer showed that a combination of quercetin, ellagic acid, and resveratrol was safe and well-tolerated. Even while PSA levels did not drop noticeably, more research is being done to see whether there may be antitumor activity.

·       One major health risk is breast cancer. In one research, women at high risk of breast cancer had their prostaglandin E2 (PGE2) production and DNA methylation examined in relation to resveratrol. According to the study, resveratrol can lower PGE2 levels and decrease the methylation of the RASSF-1α gene, both of which are linked to an increased risk of breast cancer. Furthermore, postmenopausal women's resveratrol consumption was linked to higher levels of sex steroid hormone binding globulin (SHBG) and improved estrogen metabolism, which may help prevent breast cancer [10].

·       A clinical study evaluating the safety and effectiveness of resveratrol included forty healthy participants. According to the study, resveratrol use is harmless and may even help lower levels of IGF-1 and IGFBP-3, which are connected to a number of cancer types. These findings imply that resveratrol may be useful in the clinic as a chemopreventive agent for cancer [10].

In summary, resveratrol has shown promise in cancer therapy by affecting diverse signal-transduction pathways governing the various stages of cancer development. However, additional research is imperative to ascertain the optimal dosages, treatment durations, and safety profiles of resveratrol in cancer patients. The multifaceted nature of cancer necessitates ongoing exploration of potential solutions, and resveratrol's role in this endeavor is a subject of great scientific interest.