Plant isolate dibenzyl trisulfide induces caspase-independent death in triple negative breast cancer cells derived from patients of West African descent

Patients with triple negative breast cancer (TNBC) possess tumors that lack estrogen receptor, progesterone receptor, and human epidermal growth receptor expression. While these patients traditionally receive chemotherapy to combat this aggressive breast cancer subtype, others use natural remedies. Dibenzyl trisulfide (DTS) is derived from Petiveria alliacea, a perennial shrub that grows in tropical regions of the world. Many TNBC patients residing in the tropics are of West African descent. Therefore, we evaluated the anticancer actions of DTS in TNBC cells, including those derived from patients of West African descent. We found that DTS inhibited TNBC cell viability, migration and proliferation in a dose-dependent manner. Interestingly, DTS blocked the propensity of pro-carcinogen benzo-A-pyrene to induce proliferation of immortalized breast epithelial cells. Moreover, we found that DTS induced early apoptosis in TNBC cells, which was only partially attenuated following pretreatment with pan-caspase inhibitor zVAD-fmk. Though DTS induced pro-apoptotic gene and protein expression along with PARP cleavage, it failed to produce appreciable caspase 3 cleavage and promote significant apoptotic body formation. This suggests that this plant isolate induces caspase-independent and non-apoptotic death of TNBC cells. Furthermore, DTS promoted lysosomal membrane destabilization and cathepsin B release in TNBC cells. Taken together, DTS exhibits promising chemotherapeutic and chemopreventive ability by inducing non-apoptotic TNBC cell death and thwarting TNBC progression, supporting its evaluation in clinical trials as an agent to combat TNBC among patients of West African descent. Citation Format: Jonathan Wooten, Shaniece Wooten, Cristina Araújo, Joyce Aja, Nicole Mavingire, Rupika Delgoda, Eileen Brantley. Plant isolate dibenzyl trisulfide induces caspase-independent death in triple negative breast cancer cells derived from patients of West African descent [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-110.