OZ-001 suppresses the growth of triple-negative breast cancer and pancreatic cancer via targeting STAT3 phosphorylation and calcium signaling pathway

Background Triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC) are characterized by uncontrolled tumor growth, high risk of recurrence and resistance to chemotherapy, and poor prognosis. OZ-001 is a small molecule that exhibits a unique dual mechanism of action by blocking T-type Ca ²⁺ channels and targeting signal transducer and activator of transcription 3(STAT3) activation. This characteristic shows promise in addressing the urgent need for effective treatments in TNBC and PDAC. The study aimed to elucidate the anticancer characteristics, efficacy, and underlying mechanism of action of OZ-001. The finding could provide valuable insights into its therapeutic potential for treating aggressive and poor-prognosis malignancies. Methods The anticancer activities of OZ-001 were evaluated using MDA-MB-231 human TNBC cells and MIA PaCa-2 PDAC cells. In this study, cell viability, apoptosis, protein characterization, and cell cycle analysis were done to understand the influence of OZ-001 on MDA-MB-231 and MIA PaCa-2 cells. Additionally, protein affinity and intracellular calcium measurements were measured to evaluate the functional mechanism of OZ-001 targeting STAT3 and T-type calcium channels. Further, TNBC and PDAC animal models were developed using MDA-MB-231 and MIA PaCa-2 xenograft mice to assess the anticancer effects of OZ-001. Results The study observations revealed that the OZ-001 molecule induced caspase-dependent MDA-MB-231 and MIA PaCa-2 cell death via B-cell lymphoma 2(BCL-2) family proteins. OZ-001 selectively regulated cell viability by suppressing STAT3 phosphorylation-linked genes such as survivin, Mcl-1, and Cyclin D1. Specifically, OZ-001 blocked the T-type calcium channels, which reduced intracellular calcium levels and activated cell death pathways in TNBC and PDAC. Further, oral administration of OZ-001 suppressed tumor growth in MDA-MB-231 and MIA PaCa-2 xenograft mice, which could be attributed to reduced STAT3 phosphorylation and decreased tumor growth. Conclusion The study findings revealed that OZ-001 inhibits the phosphorylation of STAT3 and T-type calcium channels against TNBC and PDAC. These findings suggest the potential therapeutic application of OZ-001 as an alternative anticancer molecule.