Procaterol Enhances Cisplatin-Induced Cytotoxicity via Apoptosis,Oxidative Stress,and Cell Cycle Arrest in Breast and Cervical Cancer Cells

Abstract

Breast and cervical cancers remain significant causes of cancer-related deaths in women, necessitating the development of effective treatments. This study investigated the repositioning potential of procaterol as a chemosensitizer to increase the efficacy of cisplatin in HeLa and MCF-7 cells. On its own, procaterol showed limited cytotoxicity; however, it significantly inhibited cell viability when combined with low doses of cisplatin. Both colony formation and cell proliferation studies showed a strong inhibition of cell growth, especially in HeLa cells. Similarly, wound-healing studies showed greater inhibition of cell migration in the presence of both drugs than with either drug alone. Live/dead assays and elevated TNF-α (tumour necrosis factor-alpha) expression confirmed apoptosis. The increased generation of reactive oxygen species suggested that HeLa cells are under oxidative stress. Flow cytometric analyses showed that procaterol induced G0/G1 arrest, cisplatin induced G2/M arrest, and the combination induced both arrests while significantly decreasing S-phase populations. Procaterol sensitized cisplatin by increasing apoptosis and oxidative stress and inducing cell cycle arrest. As an FDA-approved compound, it can be used as a cost-effective adjuvant for treating breast and cervical cancer. Additional in vivo verification and clinical trials are required to establish the translational value of this new combination for the treatment of cervical and breast cancer.