Flavonoids as Multi-Target Compounds: A Special Emphasis on their Potential as Chemo-adjuvants in Cancer Therapy

Abstract

<jats:sec> <jats:title>:</jats:title> <jats:p>Flavonoids are low molecular weight, polyphenolic phytochemicals, obtained from secondary metabolism of various plant compounds. They have a spectrum of pharmacological efficacies, including potential anticancer efficacy. Natural flavonoids are present in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids can attenuate or inhibit the initiation, promotion and progression of cancer by modulating various enzymes and receptors in diverse pathways that involve cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. Furthermore, in vitro, flavonoids have been shown to reverse multidrug resistance when used as chemo-adjuvants. Flavonoids (both natural and synthetic analogues) interact with several oncogenic targets through dependent and independent mechanisms to mediate their anticancer efficacy in different types of cancer cells.</jats:p> </jats:sec>

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

“…However, further progress in precision medicine in the twenty-first century enables an individualized approach in the context of predictive, preventive, and personalized medicine that can improve cancer management [18,[61][62][63][64][65][66]. Cancer treatment can also be improved by applying natural substances, which sensitize cancer cells to therapeutic agents [67][68][69][70].…”

“…Flavonoids exert numerous biological effects, including antioxidant, anti-inflammatory, anti-mutagenic, and anticancer activities, among others [46]. Although flavonoids have demonstrated significant anti-cancer efficacy in preclinical research [46,69,71,75,76], clinical studies evaluating the anti-cancer effects of flavonoids remain sparse. Genistein was demonstrated to be safe and tolerable in combination with chemotherapy in a recent phase I/II pilot study [43].…”

“…Other clinical trials revealed the potential of flavonoids as anticarcinogenic agents [80] and as complementary antitumor agents in colorectal cancer patients [45]. However, the significant capacity of flavonoids to improve therapeutic outcomes by improving the treatment sensitivity or reversing the resistance of cancer cells to anti-cancer therapeutic agents is currently evaluated predominantly in preclinical in vitro and in vivo research [67][68][69][70].…”

Novel Chrysin-De-Allyl PAC-1 Hybrid Analogues as Anticancer Compounds: Design, Synthesis, and Biological Evaluation

“…Flavonoids are ubiquitous naturally occurring polyphenolic compounds that are commonly found in fruits and vegetables [3]. Flavonoids comprise several classes of low molecular weight compounds, including flavanones, anthocyanidins, flavonols, flavanols, isoflavones, dihydroflavonols, and flavones [4][5][6]. Chrysin (5, 7-dihydroxyflavone, Figure 1) is a natural flavone found in many plant extracts, such as the blue passionflower, as well as in honey and propolis [7,8].…”

Anticancer Activity of Natural Compounds

“…Recent updates indicate the multitarget potential of natural products that suggest their strong therapeutic potential against various complex human diseases including cancer and hence use of natural products with multitarget potential would be of great promising therapeutic value. Natural products have showed promising anti-cancer actions via targeting deregulated signaling mechanisms underlying cancer hallmarks including drug resistance, stemness features, metabolic There has been various reports demonstrating how the bioactive molecules, derived from natural products, in combination with conventional chemotherapeutic agents enhance therapeutic outcome with minimal adverse effects (Namdeo et al, 2020;Lin et al, 2020). Generally, combination of natural products gives synergetic and or additive outcome and recently we have also showed that curcumin synergistically enhanced the anticancer action of cisplatin.…”