The Apoptotic Effects of the P300 Activator on Breast Cancer and Lung Fibroblast Cell Lines

Background: P300 is an enzyme that acetylates histones during stress. It also acetylates several non-histone proteins, including P53 which is the most important tumor suppressor gene. P53 plays an important role in the apoptosis of tumor cells. Hereby, this study describes the potency of cholera toxin B subunit as a P300 activator to induce apoptosis in a breast cancer cell line (MCF-7) and a lung fibroblast cell line (MRC-5) as a non-tumorigenic control sample. Methods: MCF-7 and MRC-5 were cultured in RPMI-1640 and treated with or without cholera toxin B subunit at the concentration of 85.43 ?mol/L, based on the half- maximal inhibitory concentration index at different times (24, 48 and 72 h). The percentage of apoptotic cells was measured by flow cytometry. Real-time quantitative RT-PCR was performed to estimate the mRNA expression of P300 in MCF-7 and MRC- 5 with cholera toxin B subunit at different times. We used the ELISA and Bradford protein techniques to detect levels of total and acetylated P53 protein generated in MCF-7 and MRC-5. Results: Our findings indicated that the cholera toxin B subunit effectively and significantly induced more apoptosis in MCF-7 compared to MRC-5. We showed that expression of P300 up-regulated by increasing the time of the cholera toxin B subunit treatment in MCF-7 but not in MRC-5. In addition, the acetylated and total P53 protein levels increased more in MCF-7 cells than in MRC-5 cells. Conclusion: Cholera toxin B subunit induced significant cell death in MCF-7, but it could be well tolerated in MRC-5. Therefore, cholera toxin B subunit can be suggested as an anti-cancer agent.