Underlying mechanism for the modulation of apoptosis induced by a new benzoindole derivative on HT-29 colon cancer cells

Abstract

Colorectal cancer is the third most common form of cancer affecting both men and women around the world. The chemical and biological studies of heterocyclic compounds have been an interesting area in pharmaceutical and medicinal chemistry. A new synthetic compound namely 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino)acrylaldehyde, abbreviated as DBID was screened for the antiproliferation effects against the colorectal cancer cell line, HT-29 and its possible mechanism of action was elucidated. To determine the IC₅₀ value, MTT assay was employed and further verified by the LDH release assay and apoptosis-inducing effect. DBID inhibited the proliferation of HT-29 cells and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HT-29 cells were detected in treated cells by using the AO/PI staining and flow cytometric analysis of Annexin V. The changes in expression of some apoptotic genes were confirmed by gene quantification using RT-PCR. The current study showed that the DBID compound exhibited chemotherapeutic activity, which was evident by significant increases in the expression and activation of caspase, up-regulation of the expression of specific apoptotic genes and exploitation of the apoptotic signaling pathways to trigger cancer cell death.