Iraninan Biology Society Journal of Cellular and Molecular Research (Iranian Journal of Biology) 2383-2738 38 4 2025 12 22 Selective Cytotoxicity and Apoptotic Mechanisms of Tilapia Piscidin 4 (TP4) in Human Prostate Cancer Cells: Insights into ROS-Dependent Apoptosis Induction Selective Cytotoxicity and Apoptotic Mechanisms of Tilapia Piscidin 4 (TP4) in Human Prostate Cancer Cells: Insights into ROS-Dependent Apoptosis Induction 345 362 2374 10.22034/cmr.2024.8274.3179 FA Rashid Alijani Ardeshir Department of marine biology, Faculty of biotechnology, Amol University of Special Modern Technologies 0000-0001-9592-0886 Dariush Gholami Department of biotechnology, Faculty of biotechnology, Amol University of Special Modern Technologies, Amol, Iran 0000-0001-9441-229X Journal Article 2023 11 08 Background and objective: The use of antimicrobial peptides in cancer treatment is a new therapeutic approach that has gained attention in scientific research for the treatment of various types of cancer. This study aimed to investigate the cytotoxic effects of the antimicrobial peptide Tilapia piscidin 4 (TP4) and elucidate its apoptotic molecular mechanisms in the human prostate cancer cell line PC3. Methods: PC3 cells were divided into three groups: untreated PC3 cells, treated cells with IC50 0.5 and IC50 0.25. After the treatment, oxidative stress indices, DNA damage measurement by Comet method and expression of genes related to apoptosis were evaluated. Results: The results demonstrated the inhibitory effect of TP4 on PC3 cell proliferation after 24 hours (IC50 = 15.50 μg/mL), while no cellular toxicity was observed in normal prostate cells (PrEC-31) at this concentration. The selectivity index (SI) exceeded 2, indicating TP4's high specificity for cancer cells. Treatment of PC3 cells with 25% and 50% of the IC50 for TP4 induced apoptosis and DNA fragmentation in PC3 cells. This apoptosis induction was accompanied by increased expression of pro-apoptotic genes (Bax, P53, and Caspase 3) and decreased expression of the anti-apoptotic gene Bcl2, increased levels of intracellular reactive oxygen species (ROS), and malondialdehyde (MDA) content, as well as decreased activity of superoxide dismutase (SOD) and catalase (CAT) enzymes compared to the control group (P<0.05). Conclusion: it can be concluded that TP4 can induce apoptosis in prostate cancer cells through an ROS-dependent pathway. Background and objective: The use of antimicrobial peptides in cancer treatment is a new therapeutic approach that has gained attention in scientific research for the treatment of various types of cancer. This study aimed to investigate the cytotoxic effects of the antimicrobial peptide Tilapia piscidin 4 (TP4) and elucidate its apoptotic molecular mechanisms in the human prostate cancer cell line PC3. Methods: PC3 cells were divided into three groups: untreated PC3 cells, treated cells with IC50 0.5 and IC50 0.25. After the treatment, oxidative stress indices, DNA damage measurement by Comet method and expression of genes related to apoptosis were evaluated. Results: The results demonstrated the inhibitory effect of TP4 on PC3 cell proliferation after 24 hours (IC50 = 15.50 μg/mL), while no cellular toxicity was observed in normal prostate cells (PrEC-31) at this concentration. The selectivity index (SI) exceeded 2, indicating TP4's high specificity for cancer cells. Treatment of PC3 cells with 25% and 50% of the IC50 for TP4 induced apoptosis and DNA fragmentation in PC3 cells. This apoptosis induction was accompanied by increased expression of pro-apoptotic genes (Bax, P53, and Caspase 3) and decreased expression of the anti-apoptotic gene Bcl2, increased levels of intracellular reactive oxygen species (ROS), and malondialdehyde (MDA) content, as well as decreased activity of superoxide dismutase (SOD) and catalase (CAT) enzymes compared to the control group (P<0.05). Conclusion: it can be concluded that TP4 can induce apoptosis in prostate cancer cells through an ROS-dependent pathway.

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