Piperine derivative, (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(2-hydroxyphenyl)penta-2,4-dienamide, exerted cytotoxic activity toward MCF-7 breast cancer cells via Apoptosis: Gene expression and biomolecular change study

Abstract

Breast cancer is one of the leading causes of mortality in women worldwide. Adverse side effects have been reported from chemotherapeutic agents of systematic therapies. Therefore, new agents are still needed for breast cancer treatment. This research aimed to investigate anticancer activity and mechanisms of a piperine derivative, named (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(2-hydroxyphenyl)penta-2,4-dienamide (1f), against MCF-7 breast cancer cell. The results show that 1f ranging from 7.5 to 60 μg/mL inhibited MCF-7 cells in dose-dependent manner with IC₅₀ values of 17.02 ± 1.74 μg/mL. It inhibited cell migration in dose and time dependent manners. In addition, it induced morphological characteristics of apoptosis and increased the level of intracellular reactive oxygen species (ROS). Phosphatidylserine (PS) exposure staining and DNA fragmentation confirmed the induction of apoptosis. 1f induced the gene expression of TP53, PTEN, and CASP9, while ESR1, BRCA1, BRCA2, PIK3CA, AKT1 CHEK2, BRIP1 and KRAS expression were decreased. STRING protein-protein interaction network and KEGG pathway analysis predicted the induction of apoptosis linked with DNA repair, estrogen receptor-α (ER-α), and PI3K/AKT signaling pathways. Moreover, Fourier transform infrared spectroscopy (FTIR) results shows that 1f reduced the lipid utilization rate and inhibited protein synthesis, resulting in the induction of apoptosis. Overall, 1f is an interesting candidate for development as an anticancer agent for breast cancer.