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Clinical trials of new drugs often face a high failure rate of approximately 45 percent due to safety and toxicity concerns. Repurposing drugs with well-established safety profiles becomes crucial in addressing this challenge. Colon cancer ranks as the third most prevalent cancer and the second leading cause of cancer related mortality worldwide. This study focuses on the RNA-binding protein pumilio1 (PUM1), a member of the PUF family involved in post-transcriptional gene expression regulation. By utilizing molecular docking techniques and FDA-approved drugs, potential inhibitors against PUM1 were identified. Notably, dolasetron and ketoprofen demonstrated promising results, exhibiting strong binding affinity, hydrophobic interactions, and favorable chemical reactivity according to Conceptual-DFT calculations. Both compounds effectively reduced cell viability, with IC50 values of 150 µM and 175 µM, respectively and shows long term inhibitory effects as seen by reduced in number of colonies. Moreover, they exhibited inhibitory effects on colon cancer stem cells, as indicated by reduced colonospheroid size and numbers. Apoptosis is induced by these compounds and has triggered activation of executioner caspase 3/7 in HCT116 cells which is evident through a caspase 3/7 assay and AO/EB staining, while the non-toxic effect of these compounds was evident from viability against non-cancerous cell line and hemolysis assay. Additionally, the treatment group showed a significant decrease in PUM1 and cancer stem cell markers expression compared to the control group. In conclusion, this study highlights the potential of targeting PUM1 as a novel approach to colon cancer treatment. Dolasetron and ketoprofen demonstrate promise as effective anti-cancer and anti-cancer stem cell drugs, inducing apoptosis in colon cancer cells through inhibition of PUM1.

Endocrine cancer is an uncontrolled growth of cells in the hormone-producing glands. Endocrine cancers include the adrenal, thyroid, parathyroid, pancreas, pituitary, and ovary malignancy. Recently, there has been an increase in the incidence of the most common endocrine cancer types, namely pancreatic and thyroid cancers. Cancer stem cells (CSCs) of endocrine tumors have received more attention due to their role in cancer progression, therapeutic resistance, and cancer relapse. Therefore, finding the natural phytochemicals that target the CSCs will help improve cancer patients' prognosis and life expectancy. Phytochemicals have also been shown to have anti-CSCs and are very effective in treating various cancer types. Curcumin is a common polyphenol found in turmeric, which has been shown to promote cellular drug accumulation and increase the effectiveness of chemotherapy. Moreover, various other phytochemicals such as resveratrol, genistein, and apigenin are effective against different endocrine cancers by regulating the CSCs. Therefore, phytochemicals have emerged as chemotherapeutics that may have significance in preventing and treating endocrine cancers.