Cinnamaldehyde potentiates cytotoxic and apoptogenic effects of doxorubicin in prostate cancer cell line

Abstract

Background and purpose: Nowadays, herbal medicine has been utilized to treat various diseases such as cancer, which showed successful therapeutic efficacy in previous studies. This study for the first time evaluated the cytotoxic potential of cinnamaldehyde (CIN) alone and in combination with doxorubicin (DOX), a well-known potent anti-tumor agent, on the proliferation of prostatic cancer cell line (PC3). Experimental approach: The cytotoxicity and apoptotic activities of CIN and DOX, either separately or together, were determined on PC3 cells by the MTT test and Annexin V/PI assay, respectively. To further investigate which apoptotic pathway participated in cell death a collection of prominent markers of apoptosis induction including caspase-3/7 activations, mitochondrial membrane potential (MMP), and phosphatidyl serine translocation were detected. Findings/Results: The different concentrations of CIN and DOX significantly inhibited the proliferation of PC3 cells in a concentration-dependent way within a 24-h treatment. In addition, the induction of apoptosis by CIN was accompanied by an increase in the activation of caspase-3/7 in PC3 cells with IC50 concentrations of 12.5 and 10 μg/mL for CIN and DOX, respectively. Moreover, the morphological observations obtained from flow cytometry MMP and caspase-3/7 activity assays, altogether, revealed the potential effect of CIN on apoptosis induced in PC3 cells by DOX. Conclusions and implications: Taken together, the current study concluded that the combination of CIN and DOX could lead to the production of a potential therapeutic agent for prostate cancer. However, further in vivo and clinical studies are still needed to validate this combination in prostate cancer therapy.

Keywords

• apoptosis
• cinnamaldehyde
• cytotoxicity
• doxorubicin
• prostate cancer