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Increasing consumption of flavonoid-rich foods-A key anticancer approach

I believe that increased con­sumption of flavonoid-rich foods is key to the fight against cancer particularly in resource-constrained settings such as ours. For this piece, I will be using materials from a paper by Kopustinekiene et al. Flavonoids As Anticancer Agents. Nutrients 2020 Feb 12;12 (2);457.

Flavonoids are polyphenolic com­pounds synthesized in plants as bioac­tive secondary metabolites responsible for their colour, flavour and phar­macological activities. Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flava­nones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-de­rived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids.

Flavonoids can scavenge free radicals, regulate cellular metabolism, and prevent oxidative stress–related diseases including cancer.

Cancer- A heterogeneous disease

Cancer is a heterogenous disease. This means that different cancer cells within the same tumour or between different tumours can show distinct morphological and phenotypic pro­files, including cellular morphology, motility, proliferation, and metastatic potential. Cancer is characterised by uncontrolled proliferation and im­paired cell cycle leading to the growth of abnormal cells that invade and metastasize to other parts of the body.

Internal and external causes

Oxidative stress, hypoxia, genet­ic mutations and lack of apoptotic function are the main internal causes of cancer, whereas the external causes are related to increased exposure to stress, pollution, smoking, radiation and ultraviolet rays.

Altered metabolism

Altered metabolism, impaired cell cycles, frequent mutations, resistance to immune response, chronic inflam­mation, formation of metastasis, and induction of angiogenesis are the main characteristics of the cancer cells.

Cancer is considered a metabolic disease determined by various degrees of mitochondrial (tiny structures with­in the cell) dysfunctions and metabolic alterations. Impaired cellular energy metabolism is a defining character­istic of cancers. Mitochondria play essential roles in cellular energy supply, regulation of metabolism, cell death signaling and reactive oxygen species (ROS) generation.

The main metabolic alterations of the tumour cells involve increased aerobic glycolysis, deregulated pH, impaired lipid metabolism, increased generation of ROS, and compromised enzyme activities. As a direct conse­quence, the extracellular environment becomes acidic and more favourable to inflammation, glutamine-driv­en lipid biosynthesis increases and upregulates the pathways involved in tumorigenesis initiation and metastasis.

The main characteristics of tumour mitochondria and tumour cells.

Tumour-cell metabolism is altered compared to normal cells due to high­ly abnormal mitochondrial functions]. Flavonoids as natural compounds revert the mitochondria to normal mode.

Flavonoids restore

Flavonoids exert a wide variety of anticancer effects: they modulate ROS-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness.

When the cellular homeostasis between the pro-oxidant activities and antioxidant defence is im­paired, the pro­duc­tion of ROS increases, and free radicals accumu­late leading to oxidative stress, development of inflammation, impaired metabolism, several degenerative diseases and cancer.

Flavonoids can directly scavenge ROS and chelate metal ions due to their ability stabilise the free radicals due to the presence of phenolic hy­droxyl groups. Indirect flavonoid anti­oxidant effects are related to activation of antioxidant enzymes, suppression of pro-oxidant enzymes, and stimulat­ing production of antioxidant enzymes and phase II detoxification enzymes

Cancer cells are resistant to apopto­sis—a programmed cell death.

Inflammation and immune sys­tem dysfunction

Chronic inflammation leads to tumour development, modulating cellular transformation, survival, proliferation, invasion, metastasis, and angiogenesis pathways. Flavonoids exert anti-inflammatory action via im­mune cell regulation, and suppression of enzymes promoting inflammation.

The immune system is a key player in protecting an organism from infections and cancer. B and T lymphocytes and macro­phages are the major cells responsible for the immu­nity. B cells secret antibodies which can attach to pathogens, mark­ing them so they are recognized and destroyed by phagocytes. T cytotoxic cells can kill tumour cells directly, and T helper cells secrete cytokines and mediators which regulate the activities of B lymphocytes and macrophages. Flavonoids have been shown to modulate directly the differentiation and count of the cells belonging to the immune system.

Chronic inflammation often pre­cedes tumour development, therefore anti-inflammatory effects of flavo­noids is very important in decreasing the inflammation and enhancing the antitumour activity of immune cells.

In tumour cells, mitochondria are usually hyperpolarised, and their membrane potential reaches 220 mV making them resistant to cell death signaling. Flavonoids induce apoptosis and decrease mitochondrial membrane potential.

Gut microbiota

The gastrointestinal tract, and espe­cially the intestinal barrier, is very im­portant in sustaining health. Intestinal epithelium, besides nutrient absorp­tion, provides a barrier con­trolling the entrance of mi­croorganisms, their metabolic products and toxins as well as toxins present in ingested foods. Due to anti-inflammatory action, flavonoids could protect the integrity of the intestinal barrier.

Flavonoids suppress the activity of gut metabolizing enzymes—α-gluco­sidase, pancreatic lipoprotein lipase and amylase. In the gastrointestinal tract lumen, the decreased activities of α-glucosidase, pancreatic lipoprotein li­pase and amylase leads to a suppressed absorption of glucose from complex carbohydrates and fatty acids from triglycerides.

Most flavonoids (except flavanols) are naturally attached to sugars as β-glycosides; therefore, they are not readily andv completely absorbed in the small intestine, and glycosylated flavonoids reach the colon where the microbiota digest the flavonoids forming phenolic acids and other metabolites, which can later be ab­sorbed. Thus, flavonoids in the colon influence the gut microbiome, whereas microbes modulate flavonoid activity and bioavailability metabolizing them and these processes are beneficial for health. Flavonoids are known to exert antimicrobial activity, inhibiting spe­cific microbes, such as pathogenic and commensal microorganisms.

The polyphenols present in cloud­berry decrease the growth of Candida albicans, Bacillus cereus, Helicobacter pylori, Campylobacter jejuni, Staphy­lococcus epidermidis, Staphylococcus aureus and Clostridium perfingens. Flavonoids affect microbial pop­ulations by changing endotoxin production, converting primary into secondary bile acids, sustaining im­mune homeostasis and participating in bioactive and nutrient absorption and metabolism, thereby regulating short-chain fatty acid formation.

Thus, ingestion of flavonoids is related to the suppression of inflam­matory markers via the downregula­tion of the transcription factor NF-κB signaling pathway in the gastrointesti­nal tract and is considered a promising strategy in therapeutic approaches preventing chronic diseases and controlling inflammation due to the modulation of the microbiota.

Conclusion

Flavonoids are natural molecules, present in human foods and beverages without the dangerous side effects of synthetic anti-cancer drugs. Flavonoids have strong positive activities in reduc­ing inflammation, modulating immune response, and supporting and restoring the normal functions of cells. Flavo­noids exert a wide range of anticancer effects and considered novel cancer chemopreventive agents. The daily intake of flavonoids as flavonoid-rich foods or flavonoid supplements induces favourable changes in the gut microbiota, decreasing the risk of cancer and normalising vital functions at cellular level. Cocoa is an excellent source of flavonoids.

DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC