Gene Expression Alterations Associated with Sanguinarine‐Induced Antiproliferative effects and Apoptosis in Triple‐Negative Breast Cancer Cells

Abstract

Sanguinarine (SAN) is a plant alkaloid found in various plants, mainly Sanguinaria canadensis. SAN has various pharmacological properties, including anti-bacterial, anti-fungal, anti-inflammatory, and anti-cancer effects. The current study investigated the mechanisms that mediated the anti-cancer effects of SAN in two triple-negative breast cancer (TNBC) cell lines; MDA-MB-231 and MDA-MB-468 cells. The data obtained suggested SAN is a potent compound in reducing cell viability and proliferation. Moreover, the results show that MDA-MB-468 cells were more sensitive than MDA-MB-231 cells to SAN. Also, SAN induced apoptosis in both cell lines by arresting cell growth. The compound arrested MDA-MB-231 cells at the Sub-G1 phase and MDA-MB-468 cells at the G2/M phase. Gene expression profiling indicated that MDA-MB-468 cells had significant transcription activation (2-4-fold) in eighteen genes. The genes activated include two members of the caspase family (caspase 1 and caspase 10), seven members of the TNF receptor superfamily (TNFRSF) such as TNFRSF10A, TNFRSF10B, TNFRSF11B, TNFRSF21, and TNFRSF25), in addition to TNFRSF1A Associated Via Death Domain (TRADD) and Fas-associated via death domain (FADD). On the other hand, in MDA-MB-231 cells, SAN was found to alter twelve five genes. The upregulated genes include Lymphotoxin Alpha (LTA; 15-fold), growth arrest and DNA damage-inducible 45 alpha (GADD45A), BCL2 Related Protein A1 (BCL2A1), BCL2-Like 11 (BCL2L11), and Bcl-2-Binding Protein Bis (BAG3). These results provide evidence that genetically different cells may respond differently to treatments, explaining the inadequate therapeutic response of some patients with advanced TNBC. The data also suggest that this plant alkaloid SAN could have therapeutic potential for TNBC patients.