Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments. Novel strategies are therefore required for better management of cancer therapy. The prime approach would be to synthesize and develop novel drugs that need extensive resources, time, and endurance to be brought into therapeutic use. The subsequent approach would be to screen the anti-cancer activity of available non-cancerous drugs. This concept of repurposing non-cancer drugs as an alternative to current cancer therapy has become popular in recent years because using existing anticancer drugs has several adverse effects. Micronutrients have also been investigated for cancer therapy due to their significant anti-cancer effects with negligible or no side effects and availability in food sources. In this paper, we discuss an ideal hypothesis for screening available non-cancerous drugs with anticancer activity, with a focus on cancer stem cells and their clinical application for cancer treatment. Further, drug repurposing and the combination of micronutrients that can target both cancers and cancer stem cells may result in a better therapeutic approach leading to maximum tumor growth control.

Background: Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. MurrayakoenigiiSpreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murrayakoenigiileaves (curry leaves), a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death.Methods: Hydro-methanolic extract of curry leaves (CLE) was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau’s method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes.Results: CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells.Conclusions: Our study suggests M.koenigiileaves to be a potent source of proteasome inhibitors that lead to cancer cell death. Therefore, identification of active component(s) from the leaf extract could lead to the development of anti-cancer agents which could be useful in the treatment of different types of cancers.

Background: Pancreatic cancer is the foremost cause of cancer-related deaths in many developed countries with a poor prognosis. With advanced disease conditions chemotherapy, surgery followed by radiation is the regimen to prolong the survival. But a complete cure is questionable. Metformin is the first-line drug used for the treatment of type 2 diabetes in the world. Aim: The study aims to assess the anti-cancer activity of metformin with the combination of micronutrient pyridoxal phosphate (PLP) in the human pancreatic cancer cell line (PANC-1). Methods: Panc1 cells were maintained in vitro cell culture conditions. The IC50 concentrations of metformin and PLP were estimated and selected by using MTT assay. Morphological changes upon treatments were observed under microscope. Distribution of cells pattern was observed with propidium iodide dye in cell cycle assay. Different phases of cell distribution were studied with apoptosis assay. Results: More morphological changes were observed with PLP followed metformin. MTT assay revelled the IC50 concentrations of metformin and PLP were 20.95 ± 0.98 mM and 5.70 ± 0.07 mM. The cell cycle assay revealed that the percentage of cells was arrested in different phases with the treatments. Apoptosis assay revelled metformin increased necrosis population to 9.9%, whereas PLP has enhanced to 14.2% apoptosis. Tumour suppressor protein p53 levels had increased to 24.8% with PLP and 3.5% with metformin. Conclusion: In conclusion, PLP has significantly induced cell cycle arrest, apoptosis and enhanced p53 protein expression but a combination of PLP with metformin drug has not synergised anti-cancer activity in human PANC1 cells.