Exploring Caspase-3 overexpression in pheochromocytoma cells: Implications for cancer therapy

Malignant pheochromocytomas are infrequent tumors that have a poorer prognosis compared to their benign counterparts. The administration of chemotherapy to patients with pheochromocytoma can result in adverse side effects and a reduced life quality. Alternative and more targeted treatment strategies, such as gene therapy significantly improve the patients' survival rate and life expectancy. Caspase-3 is a key apoptosis regulator activated by cancer treatments. Recent research shows it also influences tumor relapse and angiogenesis, complicating its role in cancer progression. Further exploration of Caspase-3's diverse functions is needed to clarify its impact on cancer development. In this study, we established Caspase-3 over expressed pheochromocytoma cell line by the use of lentiviral vector technology. Caspase 3 over expression by up to 3fold led to increase in cell proliferation by up to 12 %. Moreover, increasing in Caspase 3 level of expression resulted in more invasiveness and metastasis. By this way, the wound closure percentage for PC-12 Casp3 + cells reached 76.2 %, which is significantly higher compared to the 52.8 % observed in mock cells. Casp3 + cells were also significantly more sensitive to cisplatin than mock cells with Ic50 of 158.4 μM and 219.5uM respectively according to MTT assay which confirmed by apoptosis assay. Hence, targeting Caspase-3 as a therapeutic approach may enhance the cancer cell sensitivity to chemotherapy, but also increase the cancer cell proliferation, metastases and invasion which may works as a double edge sword. CONCLUSION: understanding the effects of Caspase 3 over expression on cancer cells could inspire innovative therapies targeting its non-apoptotic actions, potentially improving cancer treatment outcomes.