Quercetin, abbreviated as Qu, is a flavonoid found in many vegetables, fruits, and refreshments.
Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant creation and are categorized according to chemical construction into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones. Flavonoids have stimulated considerable interest recently because of their possible beneficial effects on human health-they have been described to have antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, and antioxidant actions. Epidemiological studies have revealed that the consumption of sources of flavonoids like vegetables, fruits, and tea, is linked with a low risk of cancer. Many flavonoids exercise potent anti-tumor activity by induction of apoptosis and cell cycle arrest in many cancer cell lines.
Quercetin (3,5,7,3′,4′-pentahydroxyflavone) is the main representative of the flavonoid subclass of flavonols. Because of its anti-oxidant, anti-tumor, and anti-inflammatory activity, quercetin has been considered extensively as a chemoprevention agent in various cancer models. Quercetin has been known to inhibit the proliferation of a broad range of cancers such as prostate cancer, cervical cancer, lung cancer, breast cancer, and colon cancer. Modern studies have revealed that quercetin inhibits cell proliferation by inducing apoptosis and/or cell cycle arrest.
QUERCETIN AND ITS BIOLOGICAL FUNCTIONS
Quercetin is a natural product in human food, and sufficiently in the form of glycoside in a variety of plants, fruits, and vegetables, like onion, buckwheat, and broccoli. It has been affixed to functional foods as a profitable dietary supplement and may play a part in the prevention or treatment of various diseases like cancer.
It is largely absorbed within intestinal cells in the form of glycosides, hydrolyzed into aglycone, and penetrates the intestinal lumen, and its mechanism may be linked to glucose transport. The transmutation process occurs largely in the intestines, and some can be done in the liver and some in the blood. Quercetin and its metabolites are often excreted in the intestine, and a minute portion can be excreted in the urine by the kidneys. The newest research pointed out that gut microbiota plays an influential role in generating glycosidases and enzymes, which can carry quercetin into smaller, more readily absorbed molecules. Quercetin can also be metabolized to glucuronidated, methylated, and sulfated derivatives.
Angiogenesis is one of the very crucial cancer-related processes. It has been observed that quercetin uses its anti-angiogenesis effects in different cancers. Furthermore, quercetin is proficient to guard against free radicals including smoking. Free radicals dawned from cigarette tar can impose incurable damages to erythrocyte membranes. Additionally, quercetin and its conjugate metabolites have been stated to possess the potential to protect erythrocytes against damage to the membrane resulting from smoking.
QUERCETIN AND CANCER
Notwithstanding many improvements in cancer treatment, it is still recognized as a life-threatening fatality in humans. Although chemotherapy is applied as the standard treatment for cancer, it has been explained that its usage is restricted in most cancers because of chemotherapy resistance and its potential side effects.
These days, natural compounds such as quercetin have been perceived as significant agents for arresting and healing cancer. The reason being their predictable performance, great therapeutic potential, and their feeble toxicity. It appears that quercetin plays a crucial role as an anti-proliferative and anti-cancer agent and also stimulates apoptosis. Copious studies probed the influence of isolated quercetin compounds in various cancer cell lines. Unmistakably, quercetin has controlled the proliferation of cancers such as gastric cancer (GC), breast cancer, colorectal cancer (CRC), oral cancer, liver cancer, prostate cancer, thyroid cancer, leukemia, pancreatic cancer, and lung cancer.
QUERCETIN AND GASTRO-INTESTINAL CANCERS
Quercetin significantly contained GC cell viability, migration, and invasion exercises via decreasing representation of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) proteins, which are heavily associated with GC metastasis. Quercetin could be employed as an anti-metastatic agent against GC metastasis cells by intervening with uPA/uPAR systems, AMPKα, NF-κβ, ERK1/2, and PKC-δ control.
QUERCETIN AND HAEMATOLOGICAL CANCERS
Quercetin has been also demonstrated to possess advantageous effects on hematological cancers. An investigation was carried out which explicated that quercetin hinders the proliferation of MM.1R, ARP-1, and RPMI8226 multiple myeloma cell lines by inducing apoptosis along with cycle arrest in the G2/M phase. Furthermore, the blend of quercetin with dexamethasone additional enhanced apoptosis and inhibited tumor growth. Another study reported that quercetin restrains multiple myeloma cells proliferation by down-regulating the expression of IQGAP1 and ERK activation. It has been shown that quercetin overpowers STAT3 and PI3K/AKT/mTOR pathways in primary effusion lymphoma (PEL) cells commencing the downregulation of the prosurvival cellular proteins expression, involving cMyc, cyclin D1, and c-FLIP. Besides, quercetin reduced the IL-6 and IL-10 release, ending in PEL cell death.
QUERCETIN: A NOVEL THERAPY FOR OVARIAN CANCER
Ovarian cancer is one of the most common types of women fatalities and is liable for the most deaths amongst gynecologic cancers. In this cancer, there are some dangerous factors like age, family history, late menopause, and null parity whilst with the pregnancy and breastfeeding diminish the occurrence risk.
The biology of ovarian cancer varies from that of hematogenous metastasizing tumors as ovarian cancer cells originally disseminate within the peritoneal cavity and are only outwardly invasive. Nonetheless, since the rapidly proliferating tumors shrink visceral organs and are only transiently chemosensitive, ovarian carcinoma is a life-threatening disease.
An investigation illustrated that quercetin could have a synergic effect on gefitinib anti-cancer properties on PA-1 cells, ovarian cancer originated cell line. Plus, it exposed that quercetin reduced the cell viability of PA-1 cells in a dose and time-dependent fashion. It is worth mentioning that the investigation also reported 75 μM of quercetin as an optimal dose.
Fresh indications about quercetin’s effects on heightening the sensitivity of tumor radiotherapy have exposed that quercetin could intensify the effect of radiation-induced cell death. The union of quercetin treatment with X-irradiation progressed the DNA damages and designed common apoptotic cell death, and resulted in the building of Bax level and weakening of Bcl-2 level in ovarian cancer cell lines (OV2008 and SKOV3) as compared to cells shown to quercetin or X-rays alone. Along with this, an aggregate of quercetin treatment with radiation notably suppressed the growth of tumors, followed by the installation of p53, CCAAT/enhancer-binding protein homologous protein (CHOP) that is the ER stress biomarker, and γ-H2AX. Overall, these outcomes explicated that quercetin served as a promising radiosensitizer by p53-dependent ER stress flags in the human ovarian tumor xenograft model.
Among flavonoids, quercetin (Qu) is acknowledged as a remarkable free-radical scavenging antioxidant, even if such an action greatly depends on the intracellular availability of decreased glutathione. In addition to the antioxidant activity, Qu also uses a direct, pro-apoptotic effect in tumor cells, and can indeed obstruct the growth of several human cancer cell lines at distinct phases of the cell cycle. Both these effects have been seen in a wide variety of cellular models as well as in animal models. The high toxicity exercised by Qu on cancer cells faultlessly matches with the almost full absence of any damages for normal, non-transformed cells.