Abstract 4907: Elucidating the inhibitory role of plant alkaloids in breast cancer metastasis

Abstract

Despite extremely high morbidity and mortality of >90% from metastasis, it remains one of the most challenging process for targeted therapeutic interventions. Identification and characterization of chemically active and bioavailable compounds from medicinal plants targeting the cell-signaling pathways of Cancer Stem Cells (CSCs), tumor cells and their microenvironment that abet metastasis is of great clinical significance. Hence, MCF-7; a breast cancer cell line, was treated with fractionated alkaloidal extracts from Rhazya stricta with previously documented anti-cancer activity in lung and pancreatic cancer cell lines. RNA-seq. analysis was performed for samples treated with compounds that actively inhibited cell migration in scratch assay to further substantiate their anti-metastatic role at the cellular and molecular level. Genomic data corroborated the presence of anti-metastatic compounds that actively down-regulated genes involved in promoting metastasis (CDC6), cell migration (KIF23, DLGAP5), invasion and CSCs’ expansion (PTTG1). We also found down-regulation of GAS1 expression, an enhancer of Hedgehog signaling pathway. To our knowledge, this study, first of its kind, sets precedence in exploiting the anti-metastatic potential of these compounds. Further proof of concept studies in mouse models of breast cancer to establish precise mechanism-of-action(s), would certainly open up avenues for the development of new chemical entities (NCEs), targeting metastasis regulating gene(s) with precision. Citation Format: Waqas Iqbal, Saleh Alkarim, Jamal S. Sabir, Roop S. Bora, Kulvinder S. Saini. Elucidating the inhibitory role of plant alkaloids in breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4907. doi:10.1158/1538-7445.AM2017-4907