Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update

Abstract

Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed.

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericum�ascyron L.

“…As an antitumor agent, it acts on virtually all stages of carcinogenesis, from initiation to invasion and metastasis, and may undermine the basis of the development and maintenance of tumors. Previous studies have demonstrated that the anti-proliferative and apoptotic processes caused by Q were mainly mediated by the phosphoinositide 3-kinase/protein kinase B pathway in HeLa cells (2,25,26). K was first confirmed as an antioxidant in Aconitum paniculatum (27).…”

Geroprotective and Radioprotective Activity of Quercetin, (-)-Epicatechin, and Ibuprofen in Drosophila melanogaster

“…Firstly, well-known anti-oxidant properties of quercetin and (-)-epicatechin provide the protection of cellular macromolecules from damages and predict the mitochondrial dysfunction (Khan et al, 2016). In this way, studied drugs demonstrated benefit action against the development of aging-related pathologies including neurodegeneration (Shay et al, 2015; Barreca et al, 2016; Elumalai and Lakshmi, 2016), cardiovascular and liver diseases (Ansar et al, 2016; Cheserek et al, 2016), diabetes (Shay et al, 2015; Haddad and Eid, 2016), cancer (Shay et al, 2015; Khan et al, 2016). …”

Quercetin: A functional dietary flavonoid with potential chemo‐preventive properties in colorectal cancer

“…From the chemical point of view, quercetin is able to interact with phosphatidylinositol 3‐kinase (PI3K)‐Akt/PKB (protein kinase B), SAPK/ERK kinase 1 (SEK1), c‐Jun N‐terminal kinase 1/2 (JNK1/2), extracellular signal‐regulated kinase (ERK) kinase (MEK1), ERK1/2, Raf, and mitogen‐activated protein kinase (MAPK) (GULATI, LAUDET, ZOHRABIAN, Murali, & JHANWAR‐UNIYAL, ; Kumamoto, Fujii, & Hou, ; Lee & Lee, ). This binding is reported to achieve by hydrogen bonding between amino acid residues of kinases and various hydroxyl groups of quercetin (Khan, Niaz et al, ; Raman, Chen, & Cobb, ). All mentioned kinases and their signaling pathways are involved in inducing reprogramming events related to gene expression through phosphorylation of multiple key intracellular molecular targets, and thus potentiate cellular growth, spreading, and antiapoptotic properties.…”

“…Quercetin is one of the most important and well‐studied flavonoids abundant in various types of vegetables and fruits, including capers, lovage, dill, cilantro, broccoli, onions, various berries (e.g., chokeberries, cranberries, and lingonberries), and tea (Sak, ). In addition, quercetin has been shown to effectively inhibit cancer growth (Khan, Niaz et al, ). The specific and exact mechanisms responsible for the antitumoral effect of quercetin are not quite understood, but inhibition of tyrosine kinases of mitogenic signal transduction pathways, modification of important signaling pathways involved in the tumorigenesis, interplay with specific receptors and proteins, are among the most acceptable mechanisms for the anticancer effects of this flavonoid (Khan, Paul et al, ).…”

“…In addition, TEF treatment enhanced the expression of pro‐apoptotic factors and decreased the level of Bcl2. TEF led to activation of mitochondrial JNK, which has a pivotal function in oxidative stress and caspase mediated apoptosis (Khan, Niaz et al, ). Another potential mechanism for pro‐apoptotic effects of quercetin is the induction of the accumulation of death receptors in lipid rafts.…”