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Objective: Prostate cancer is one of the most commonly diagnosed cancer types in men and many people die every year due to recurring or acquiring aggressive forms of prostate cancer. Numerous chemotherapeutics, such as paclitaxel and doxorubicin are commonly used in the treatment of prostate cancer. However, acquired resistance to chemotherapeutics and broad systemic side effects substantially limit their usage. Curcumin is one of the most examined phytochemicals of the herbal remedy turmeric. Herein, we aimed to investigate the synergistic capability of curcumin on doxorubicin in prostate cancer cells. Method: The human adenocarcinoma cell line LNCaP was used in cell culture studies. Cell viability was examined by WST-1 assay. The protein expression levels of Beclin1, p62/SQSTM1, LC3-I/II, Hrd1, gp78, polyubiquitin, PERK, eIF2a, phospho-(Ser51) eIF2a, IRE1a, XBP-1s, PARP-1, caspase-3, AR, PSA, c-Myc, E-cadherin, N-cadherin and VEGF-A were investigated by immunoblotting assay. Results: Our data indicated that co-administration of curcumin with doxorubicin significantly improved the cytotoxic effect of doxorubicin in LNCaP cells. Also, the combination of curcumin and doxorubicin reduced the autophagic flux and remarkably induced endoplasmic reticulum-associated-degradation (ERAD) and unfolded protein response (UPR) signaling. Also, activation of apoptotic proteins PARP-1 and caspase-3 were strongly enhanced by combined treatment in a dose-dependent manner. Moreover, combined treatment markedly decreased levels of AR, PSA, c-Myc and VEGF-A proteins. Additionally, the epithelial-mesenchymal transition (EMT) was reduced by decreasing N-cadherin and increasing E-cadherin protein levels. Conclusion: Present data strongly suggest that curcumin synergistically improves the anti-cancer features of doxorubicin in prostate cancer cells. This study will be an important guide for testing the effects of the combined treatment of curcumin and doxorubicin in xenograft animal models with prostate tumors. |
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