A document by Mohammad Yassin Zamanian. Click on the document to view its contents.

A document by Mohammad Yassin Zamanian. Click on the document to view its contents.

Metformin (MET) is a preferred drug for the treatment of type 2 diabetes mellitus. Recent studies show that apart from its blood glucose-lowering effects, it also inhibits the development of various tumours, by inducing autophagy. Various studies have confirmed the inhibitory effects of MET on cancer cell lines’ propagation, migration, and invasion. The objective of the study was to comprehensively review the potential of MET as an anticancer agent, particularly focusing on its ability to induce autophagy and inhibit the development and progression of various tumors. The study aimed to explore the inhibitory effects of MET on cancer cell proliferation, migration, and invasion, and its impact on key signaling pathways such as AMPK, mTOR, and PI3K. This review noted that MET exerts its anticancer effects by regulating key signalling pathways such as phosphoinositide 3-kinase (PI3K), LC3-I and LC3-II, Beclin-1, p53, and the autophagy-related gene (ATG), inhibiting the mTOR protein, downregulating the expression of p62/SQSTM1, and blockage of the cell cycle at the G0/G1. Moreover, MET can stimulate autophagy through pathways associated with the 5′ adenosine monophosphate-activated protein kinase (AMPK), thereby inhibiting he development and progression of various human cancers, including hepatocellular carcinoma, prostate cancer, pancreatic cancer, osteosarcoma, myeloma, and non-small cell lung cancer. In summary, this detailed review provides a framework for further investigations that may appraise the autophagy-induced anticancer potential of MET and its repurposing for cancer treatment.

Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, growth factors, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of MDM2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as Smac/DIABLO and cytochrome c. Furthermore, fisetin inhibits the COX2 and Wnt/EGFR/NF-ĸB signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of CDK2 and CDK4, reducing Rb phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2F-1 and CDC2 protein levels. Additionally, fisetin has various effects on CRC cells, including inhibiting the phosphorylation of YB-1 and RSK, promoting the phosphorylation of ERK1/2, and disrupting the repair process of DSBs. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of PIK3CA-mutant CRC, resulting in a reduction of PI3K expression, AKT phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

Breast cancer (BC) has emerged as the fifth most prevalent cause of cancer-related morbidity, prompting considerable interest from researchers due to its increased malignancy and resistance to drugs. Traditional chemotherapy methods have demonstrated limited effectiveness in treating all BC subtypes, underscoring the pressing demand for innovative therapeutic strategies or medications. Curcumin, a bioactive substance extracted from Curcuma longa, has been widely examined for its potential as an oncology drug. Research indicates that turmeric extract and its derivatives effectively inhibit STAT3, resulting in downstream effects like reducing cancer cell growth, triggering cell death, and preventing metastasis. The research on curcumin’s impact on the STAT3 pathway in BC demonstrated that curcumin effectively inhibits STAT3, leading to downstream effects such as the downregulation of Bcl-xL, Bcl-2, and Survivin, and the induction of apoptosis in H-Ras MCF10A cells. Additionally, it showed curcumin’s ability to hinder proliferation and anchorage-independent cell growth. The research also examined the effects of curcumin derivatives, like FLLL11, FLLL12, hydrazinocurcumin (HC), and GO-Y030, on STAT3 inhibition and their potential as therapeutic agents for BC. Observed results indicated the promise of curcumin and its derivatives in targeting the STAT3 signaling pathway for BC therapy.