Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer

Abstract

Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restrict the administration of available cancer therapies. Thus, developing novel therapeutic agents are required towards a simultaneous targeting of major dysregulated signaling mediators in cancer etiology, while possessing lower side effects. In this line, the plant kingdom is introduced as a rich source of active phytochemicals. The secondary metabolites produced by plants could potentially regulate several dysregulated pathways in cancer. Among the secondary metabolites, flavonoids are hopeful phytochemicals with established biological activities and minimal side effects. Flavonoids inhibit B-cell lymphoma 2 (Bcl-2) via the p53 signaling pathway, which is a significant apoptotic target in many cancer types, hence suppressing a major dysregulated pathway in cancer. To date, there have been no studies reported which extensively highlight the role of flavonoids and especially the different classes of flavonoids in the modulation of Bcl-2 in the P53 signaling pathway. Herein, we discuss the modulation of Bcl-2 in the p53 signaling pathway by different classes of flavonoids and highlight different mechanisms through which this modulation can occur. This study will provide a rationale for the use of flavonoids against different cancers paving a new mechanistic-based approach to cancer therapy.

Systems Pharmacology-Based Strategy to Investigate the Mechanism of Ruangan Lidan Decoction for Treatment of Hepatocellular Carcinoma

“…p53 signaling pathway is a significant apoptotic target in many cancer types. It has been proved that activation of p53 signaling pathway can control proliferation and trigger apoptosis of HCC cells [ 41 , 42 ]. Furthermore, estrogen signaling pathway was reported to protect the occurrence and development of HCC.…”

Identification of epigenetic dysregulation gene markers and immune landscape in kidney renal clear cell carcinoma by comprehensive genomic analysis

“…On the other hand, as the RiskScore changed, the pathways involved in tumor occurrence and progression were different. For example, we found that among the higher-scored pathways, the enrichment score of pathways such as P53 signaling pathway ( 71 ) increased with the increase of RiskScore, while the enrichment score of metabolic pathways such as fatty acid metabolism ( 72 ), glycolysis gluconeogenesis ( 73 ), galactose metabolism ( 74 ) decreased with the increase of RiskScore. Previous literature reports have shown that these pathways are all involved in tumor progression, but they may play different roles in different tumors, and this also requires follow-up research for verification.…”

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

“…The former includes B-cell lymphoma-extra-large (Bcl-xL), Bcl-2, and myeloid-cell leukemia 1 (Mcl-1), while the latter includes Bcl-2-associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), and BH3. Bak and Bax enhance the formation of MAC, while Mcl-1, Bcl-2, and Bcl-xL inhibit its formation ( 34 ). Apart from the established roles of Bak and Bax in apoptosis, the ratio of pro-apoptotic/anti-apoptotic proteins is what governs apoptosis, rather than individual protein expression.…”