Abstract C126: Plant isolate dibenzyl trisulfide potently inhibits cytochrome P450 1 enzyme activity and the growth of breast cancer cells derived from African American patients

Abstract

Abstract Triple-negative breast cancer (TNBC), characterized by tumors that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), carries a poor prognosis. African American women develop TNBC at disproportionately higher rates than women of other ethnic groups. Dibenzyl trisulfide (DTS), found expressed in the Jamaican plant Petiveria alliacea, has been shown to inhibit the growth of several cancer types. However, little is known about whether this plant isolate displays anticancer activity in TNBC cells from African American patients or modulates cytochrome P450 1 (CYP1) enzyme activity. This work, as part of an ongoing ethnopharmacology-based bioactivity screening, was designed to fill this deficit. African American TNBC (AA-TNBC) cells HCC1806 and MDA-MB-468 were treated with varying concentrations of DTS for 48 h and cell viability was assessed using the Alamar Blue assay. DTS potently inhibited the growth of HCC1806 and MDA-MB-468 cells, producing IC50 values of 10.6 ± 1.2μM and 10.3 ± 2.0μM, respectively. Additionally, we discovered that DTS induced apoptosis in these cells. Furthermore, we investigated the ability DTS to impact the activities of the CYP1 family of enzymes, which are known to convert procarcinogens to carcinogens. The IC50 values obtained for CYPs 1A1, 1A2 and 1B1 were 1.68 ± 0.3μM, 1.9 ± 0.2μM and 1.29 ± 0.3μM, respectively. These data indicate DTS exhibits potent inhibition of the activities of these enzymes. In particular, DTS was able to bind to CYP1A2 in accordance with irreversible kinetics. In addition, DTS reduced CYP1 mRNA expression in both cell lines. Our findings provide a rationale for in vivo evaluations of DTS as a potential candidate for chemoprevention and for treating AA-TNBC patients. Citation Format: Jonathan V. Wooten, Shaniece Wauchope, Nicole Mavingire, Petreena Campbell, JéAnn Watson, Maxine Gossell-Williams, Rupika Delgoda, Eileen Brantley. Plant isolate dibenzyl trisulfide potently inhibits cytochrome P450 1 enzyme activity and the growth of breast cancer cells derived from African American patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C126.