Research Progress in Flavonoids as Potential Anticancer Drug Including Synergy with Other Approaches

Abstract

Background: In cancer chemotherapy, conventional drugs aim to target the rapidly growing and dividing cells at the early stages. However, at an advanced stage, cancer cells become less susceptible because of the multidrug resistance and the recruitment of alternative salvage pathways for their survival. Besides, owing to target non-selectivity, healthy proliferating cells also become vulnerable to the damage. The combination therapies offered using flavonoids to cure cancer not only exert an additive effect against cancer cells by targetting supplementary cell carnage pathways but also hampers the drug resistance mechanisms. Thus, the review aims to discuss the potential and pharmacokinetic limitations of flavonoids in cancer treatment. Further successful synergistic studies reported using flavonoids to treat cancer has been described along with potential drug delivery systems. Methods: A literature search was done by searching various online databases like Pubmed, Scopus, and Google Scholar with the specific keywords like “Anticancer drugs,” “flavonoids,” “oncology research,” and “pharmacokinetics.” Results: Dietary phytochemicals, mainly flavonoids, hinder cell signalling responsible for multidrug resistance and cancer progression, primarily targeting cancer cells sparing normal cells. Such properties establish flavonoids as a potential candidate for synergistic therapy. However, due to low absorption and high metabolism rates, the bioavailability of flavonoids becomes a challenge. Such challenges may be overcome using novel approaches like derivatization, and single or co-delivery nano-complexes of flavonoids with conventional drugs. These new approaches may improve the pharmacokinetic and pharmacodynamic of flavonoids. Conclusion: This review highlights the application of flavonoids as a potential anticancer phytochemical class in combination with known anti-cancer drugs/nanoparticles. It also discusses flavonoid’s pharmacokinetics and pharmacodynamics issues and ways to overcome such issues. Moreover, it covers successful methodologies employed to establish flavonoids as a safe and effective phytochemical class for cancer treatment.

Paclitaxel-Containing Extract Exerts Anti-Cancer Activity through Oral Administration in A549-Xenografted BALB/C Nude Mice: Synergistic Effect between Paclitaxel and Flavonoids or Lignoids

“…Therefore, this finding indicates that other action mechanisms may contribute to the efficacy of the HDS-1 extract beyond bioenhancers for paclitaxel. According to previous findings, two possibilities are posed as follow: Taxus-derived taxane compounds may contribute to the in vivo anti-cancer effect due to the cytotoxicity property [ 57 ], or flavonoids or lignoids may exert a synergistic effect to enhance PTX's efficacy [ 58 , 59 ]]. The latter hypothesis is confirmed by the MTT assay in our investigation, and we find that HDS-2 (flavonoids) and HDS-3 (lignoids) exert a synergistic effect with paclitaxel toward A549 growth in vitro .…”

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach

“…Apoptosis, often known as cell death, is the result of an irreversible halt in the cell cycle. By interrupting the cell cycle during the S phase, RES could delay cell cycle progression and limit the development of rat C6 glioma cells [ 125 ]. Oncogenic microRNAs (miRs) such as miR-19, miR-21, and miR-30a-5p were shown to be repressed in glioma cells, which was connected to alterations in the expression of their target genes such as p53, NF-KB, EGFR, STAT3, COX-2, and the PI3K/AKT/mTOR signaling pathway.…”

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].…”

“…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].…”