• Curcumin modulates miR-148a/MSK1/IRS1 axis to increase the chemosensitivity of CD44-positive prostate cancer cells to paclitaxel
  • Mohammad Amin Vatankhah,1 Reza Panahizadeh,2 Mohammad Rahim Vakili,3 Farhad Jeddi,4 Kazem Nejati-koshki,5 Sina Seifi Mansour,6,*
    1. Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
    2. Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
    3. Department of Surgery, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
    4. Department of Medical Genetics and Pathology, Ardabil University of Medical Sciences, Ardabil, Iran
    5. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
    6. Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran


  • Introduction: Prostate cancer (PC) is the most frequent cancer and second most common cause of cancer-related death in men. PC is commonly treated with radiotherapy, chemotherapy, and hormone therapy. Paclitaxel inhibits cancer cell proliferation in PC cells. Paclitaxel can also stop the cell cycle from progressing to the G2/M phase and prevent microtubular depolymerization by binding to free tubulin. However, paclitaxel resistance is a major challenge in advanced PC. Curcumin, a natural antioxidant, has been demonstrated to have cytotoxic effects on cancer stem cells (CSCs). Curcumin also upregulates of tumor suppressor miRNAs such as miR-205, miR-143, and miR-208 while silencing oncomirs such as miR-21, miR-14, and miR-183. The goal of this study is to explore if curcumin can help lower chemoresistance to paclitaxel through the regulation of miR-148a-mediated apoptosis in prostate CSCs.
  • Methods: drugs and reagents were bought from Sigma-Aldrich(St. Louis, MO, USA). Paclitaxel and curcumin were suspended in RPMI and kept at -20º C. We used mini-MACS to enrich CD44+ CSCs from the PC3 cell line, which was verified by immunocytochemistry. The MTT assay and DAPi labeling were used to determine cell survival. The expression of P-glycoprotein protein (P-gp) and CD44 proteins was determined by immunohistochemistry. Real-time PCR was used to evaluate the regulatory effects of curcumin and paclitaxel on miR-148a and its target genes.
  • Results: Pre-treatment of CD44+cells with curcumin significantly reduced the IC50 value and increased apoptosis rate in CD44+cells compared to paclitaxel alone. In addition, our results found that the co-treatment of carcumin and paclitaxel attenuated the expression of CD44 and P-gp compared to paclitaxel alone. On other hand, Curcumin and paclitaxel combination also enhaced miR-148a levels and down-regulated the levels of its target genes MSK1 and IRS1.
  • Conclusion: Curcumin improves the paclitaxel sensitivity in CD44+ prostate cancer cells by raising miR-148a expression and inhibiting MSK1 and IRS1.
  • Keywords: prostate cancer - cancer stem cells - curcumin - paclitaxel - miR-148a