A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells

Abstract

Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.

Leptospermum extract (QV0) suppresses pleural mesothelioma tumour growthin vitroandin vivoby mitochondrial dysfunction associated apoptosis

“…Of note, there are over 30 major individual compounds observed from Figure S1, however there are only two compounds identified: Quercetin and Kaempferol. These compounds are known to induce cytotoxic effects on cancer cells through several mechanisms, such as apoptosis, cell cycle arrest at the G2/M phase, and downregulation of epithelial-mesenchymal transition (EMT)related markers 29,30 . Over 28 individual compounds are yet to be identified and tested for their anti-cancer properties.…”

Molecular identification, characterization, and antagonistic activity profiling of Bacillus cereus LOCK 1002 along with the in-silico analysis of its presumptive bacteriocins

“…Along with B. cereus , all of these bacteriocins from different Bacillus strains can be highly important in promoting immunological feedback against pathogenic diseases [ 65 ]. Antimicrobial peptides are reported to have significant effects in suppressing microbial infections and the ROS-mediated metabolism of cancer stem cells [ 66 ], where they may be synthesized as novel AMPs for experimental applications [ 67 , 68 ].…”

Biflavonoid quercetin protects against cyclophosphamide–induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity

“…Studies (9)(10)(11)(12)(13)(14)(15) have continued to support the opinion that a number plants and plant bioactive compounds posses (in addition to their antioxidant and antiinflammatory properties) significant anticancer activity in both in-vitro and in-vivo scenarios. Some flavonoids like curcumin and quercetin have also been reported to possess chemopreventive properties through their antioxidant properties; and ability to induce cell-cycle arrest, cell growth and apoptosis (16).There is also recent evidence of the antiproliferative effects of quercetin (either alone or in combination with other flavonoids) in different cancer models (17)(18)(19)(20). The main goal of a number of these studies is to provide ample evidence supporting the possible use of plant and plant flavonoids as novel therapies in cancer prevention and treatment.…”

“…Some flavonoids like curcumin and quercetin have also been reported to possess chemopreventive properties through their antioxidant properties; and ability to induce cell-cycle arrest, cell growth and apoptosis (16). There is also recent evidence of the antiproliferative effects of quercetin (either alone or in combination with other flavonoids) in different cancer models (17–20). The main goal of a number of these studies is to provide ample evidence supporting the possible use of plant and plant flavonoids as novel therapies in cancer prevention and treatment.…”