Even though the role of autophagy is largely unknown in cancer development, there are evidence demonstrating autophagy is involved in multiple events of TC progression, including tumorigenesis, CSC maintenance, cell growth, migration and invasion, cell death as well as therapeutic resistance .
And p62 knockout is a method to inhibit tumor growth, which not only restrains autophagy via the AKT/AMPK/mTOR pathway in TPC-1 cells, but also regulates cell proliferation and apoptosis [found p62 reduction was associated with PEST-containing nuclear protein upregulation in TPC-1 and ARO cells, resulting in enhanced autophagy and decreased tumor volume in vivo.
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Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing - Journal of Translational MedicineMetformin is a well-known anti-diabetic drug that has been repurposed for several emerging applications, including as an anti-cancer agent. It boasts the distinct advantages of an excellent safety and tolerability profile and high cost-effectiveness at less than one US dollar per daily dose. Epidemiological evidence reveals that metformin reduces the risk of cancer and decreases cancer-related mortality in patients with diabetes; however, the exact mechanisms are not well understood. Energy metabolism may be central to the mechanism of action. Based on altering whole-body energy metabolism or cellular state, metformin’s modes of action can be divided into two broad, non-mutually exclusive categories: “direct effects”, which induce a direct effect on cancer cells, independent of blood glucose and insulin levels, and “indirect effects” that arise from systemic metabolic changes depending on blood glucose and insulin levels. In this review, we summarize an updated account of the current knowledge on metformin antitumor action, elaborate on the underlying mechanisms in terms of the hallmarks of cancer, and propose potential applications for repurposing metformin for cancer therapeutics.
Source: BioMedCentral - 🏆 22. / 71 Read more »
Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing - Journal of Translational MedicineMetformin is a well-known anti-diabetic drug that has been repurposed for several emerging applications, including as an anti-cancer agent. It boasts the distinct advantages of an excellent safety and tolerability profile and high cost-effectiveness at less than one US dollar per daily dose. Epidemiological evidence reveals that metformin reduces the risk of cancer and decreases cancer-related mortality in patients with diabetes; however, the exact mechanisms are not well understood. Energy metabolism may be central to the mechanism of action. Based on altering whole-body energy metabolism or cellular state, metformin’s modes of action can be divided into two broad, non-mutually exclusive categories: “direct effects”, which induce a direct effect on cancer cells, independent of blood glucose and insulin levels, and “indirect effects” that arise from systemic metabolic changes depending on blood glucose and insulin levels. In this review, we summarize an updated account of the current knowledge on metformin antitumor action, elaborate on the underlying mechanisms in terms of the hallmarks of cancer, and propose potential applications for repurposing metformin for cancer therapeutics.
Source: BioMedCentral - 🏆 22. / 71 Read more »