In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

https://www.mdpi.com/2072-6694/12/7/1985/pdf

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Flavonoids represent an important group of bioactive compounds derived from plant-based foods and beverages with known biological activity in cells. From the modulation of inflammation to the inhibition of cell proliferation, flavonoids have been described as important therapeutic adjuvants against several diseases, including diabetes, arteriosclerosis, neurological disorders, and cancer. Cancer is a complex and multifactor disease that has been studied for years however, its prevention is still one of the best known and efficient factors impacting the epidemiology of the disease. In the molecular and cellular context, some of the mechanisms underlying the oncogenesis and the progression of the disease are understood, known as the hallmarks of cancer. In this text, we review important molecular signaling pathways, including inflammation, immunity, redox metabolism, cell growth, autophagy, apoptosis, and cell cycle, and analyze the known mechanisms of action of flavonoids in cancer. The current literature provides enough evidence supporting that flavonoids may be important adjuvants in cancer therapy, highlighting the importance of healthy and balanced diets to prevent the onset and progression of the disease.

The Hallmarks of Flavonoids in Cancer

The Brassicaceae family, known as cruciferous vegetables, includes many economically important species, mainly edible oil plants, vegetable species, spice plants, and feed plants. Cruciferous vegetables are foods rich in nutritive composition and are also a good source of dietary fiber. Besides, cruciferous vegetables contain various bioactive chemicals known as glucosinolates and S-methyl cysteine sulfoxide, including sulphur-containing cancer-protective chemicals. Numerous studies have reported that daily intake of sulphurous vegetables helps prevent cancer formation and reduces cancer incidence, especially in colorectal cancer, through various mechanisms. The potential mechanisms of these compounds in preventing cancer in experimental studies are as follows: protecting cells against DNA damage, inactivating carcinogenic substances, showing antiviral and antibacterial effects, triggering apoptosis in cells with disrupted structure, inhibiting tumour cell migration causing metastasis and the development of tumour-feeding vessels (angiogenesis). These beneficial anticancer effects of cruciferous vegetables are generally associated with glucosinolates in their composition and some secondary metabolites, as well as other phenolic compounds, seed oils, and dietary fiber in the literature. This review aims to examine to the roles of cruciferous vegetables and their important bioactive metabolites in the prevention and treatment of colorectal cancer.

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Cruciferous Vegetables and Their Bioactive Metabolites: from Prevention to Novel Therapies of Colorectal Cancer

Polyphenols in fermented apple juice: Beneficial effects on human health

Gallic acid for cancer therapy: Molecular mechanisms and boosting efficacy by nanoscopical delivery.

Background Quercetin is a flavonol from the flavonoid group of polyphenols, which positively affects human health due to its anti-cancer, anti-inflammatory, anti-microbial and cardioprotective effects. The effects of phenolic compounds, including quercetin, on programmed cell death and cellular senescence, have been the subject of research in recent years. Objective In this study, we aimed to investigate the effects of quercetin on cell viability, apoptosis and cellular senescence in primary (Colo-320) and metastatic (Colo-741) colon adenocarcinoma cell lines. Methods Cytotoxicity was analyzed via MTT assay in Colo-320 and Colo-741 cell lines. After quercetin treatment, cell ularsenescence and apoptosis were evaluated by TUNEL staining, X-Gal staining and indirect peroxidase technique for immunocytochemical analysis of related proteins such as Bax, Bcl-2, caspase-3, Hsp27, Lamin B1, p16, cyclin B1. Results The effective dose for inhibition of cell growth in both cell lines was determined to be 25μg/ml quercetin for 48 hours. Increased Baximmunoreactivityfollowingquercetin treatment was significant in both Colo-320 and Colo-741 cell lines, but decreased Bcl-2 immunoreactivitywas significant only in theColo-320 primary cell line. In addition, after quercetin administration, the number of TUNEL positive cells and, immunoreactivities for p16, Lamin B1 and cyclin B1 in both Colo-320 and Colo-741 cells increased. Conclusion Our results suggest that quercetin may only induce apoptosis in primary colon cancer cells. Furthermore, quercetin also triggered senescence in colon cancer cells, but some cells remained alive, suggesting that colon cancer cells might have escaped from senescence.

Quercetin-Mediated Apoptosis and Cellular Senescence in Human Colon Cancer.

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A Review: Are Some Diet Models Beneficial or Harmful for Type 2 Diabetes Mellitus?

The anti-carcinogenic effects of polyphenols have been demonstrated over the years. Polyphenols can show anti-carcinogenic effects by providing signal transduction related to cancerous cell growth, suppression of oncogene expression, arachidonic acid metabolism, inhibition of pro-inflammatory pathways, triggering apoptotic cell death, and inhibition of angiogenesis. The capacity of phenolic compounds due to their effects on many signaling pathways in cells might indicate the potential use of polyphenols as anti-carcinogenic agents. An important and well-studied polyphenol, quercetin, has been shown to have anti-inflammatory and anti-carcinogenic effects. Apoptosis is activated by many intracellular and extracellular signals through two main signaling pathways; the extrinsic pathway and the intrinsic pathway, and regulated by many proteins. In addition to the anti-inflammatory effect of quercetin, its anti-carcinogenic effect is a topic of interest. Quercetin has the potential to induce apoptosis via the mitochondrial apoptotic pathway by causing changes in the mitochondrial membrane potential. In addition, quercetin also induces apoptosis through the activation of p53, increasing the expression of pro-apoptotic molecules such as Bax, caspase-3, caspase-9, and inhibition of anti-apoptotic proteins such as Bcl-2. In conclusion, the pro-apoptotic and anti-cancer effects of quercetin, its potential for use as a component of cancer therapy might be suggested as an alternative to other colon cancer treatments.

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Serpil Özsoy

Papers

Quercetin-Mediated Apoptosis and Cellular Senescence in Human Colon Cancer.

A Review: Are Some Diet Models Beneficial or Harmful for Type 2 Diabetes Mellitus?

Quercetin: A Phytochemical with Pro-Apoptotic Effects in Colon Cancer Cells