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.

Peptic ulcer disease is a common gastrointestinal disorder. The current treatment for gastric ulcers (GUs) is pharmacological interventions including antacids, mucosal defensive agents, H2-receptor blockers, proton pump inhibitors (PPIs) as well as antibiotics targeting H. pylori infections. Additionally, there has been an increasing focus on the application of natural treatments, such as pomegranate extracts, which have significant potential in the prevention and management of GUs. The therapeutic effects of pomegranate (Punica granatum) on GUs include its ability to inhibit ulcer formation, reduce gastric acidity, and promote the healing of gastric mucosal lesions. This is attributed to the antioxidant, anti-inflammatory, and antimicrobial properties of the active constituents in pomegranate such as polyphenols, flavonoids, tannins, and anthocyanins. The results of this study showed that pomegranate extracts could significantly suppress gastric ulceration, reduce tissue lipid peroxidation, and enhance the levels of antioxidative enzymes. Pomegranate exerts its anti-inflammatory effects through the suppression of pro-inflammatory cytokine synthesis, including TNF-α, IL-1β, and IL-6. Additionally, pomegranate extracts increase the production of gastric mucosal protective factors such as PGE2 and NO, and have antimicrobial activity against H. pylori. Overall, while pomegranate showed promise as a natural remedy for the prevention and management of GUs, further research is needed to optimize its therapeutic efficacy.

Non-melanoma skin cancer (NMSC) encompasses various skin malignancies, primarily basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Extended exposure to environmental elements, particularly solar ultraviolet (UV) radiation, triggers oxidative stress in skin tissues, resulting in DNA damage that is instrumental in the initiation and progression of NMSC. The imbalance between pro-inflammatory and anti-inflammatory cytokines plays a significant role in the development and progression of skin cancer. Resveratrol (RES), an organic phytoalexin present in grape skins and seeds, demonstrates promising chemopreventive and anti-neoplastic capabilities against NMSC. This research revealed that the synergistic lipid-nanocarrier incorporating RES and 5-FU showed significantly enhanced effectiveness in curtailing the proliferation of malignant cells, notably in the A431 cell line, in comparison to traditional formulations. Moreover, the study illustrated that the RES and 5-FU amalgamation exerted a combined effect in hindering cellular proliferation and triggering apoptosis in cancerous cells, as evidenced in both in vitro and in vivo experiments. Furthermore, RES is known for its antioxidant attributes, which may alleviate the impact of ROS triggered by UV exposure, thus diminishing DNA impairment and mutations. These observations imply that RES might offer chemopreventive benefits for NMSC through its role in apoptosis and mitigating oxidative stress. This research offers critical insights into the prospective utility of RES as a safer, more effective intervention for NMSC, though additional investigations are required to thoroughly decipher the underlying molecular mechanisms and clinical implications.

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.