Caffeic acid phenethyl ester mediates apoptosis in serum‐starved HT29 colon cancer cells through modulation of heat shock proteins and MAPK pathways

Author:

Yahya Showket1ORCID,Sulaiman Mahaboob Khan2,Sudhandiran Ganapasam1

Affiliation:

1. Cell Biology Laboratory, Department of Biochemistry, University of Madras Guindy Campus Chennai India

2. Fatima College of Health Sciences Abu Dhabi UAE

Abstract

AbstractColorectal cancer (CRC) is among the most prevalent gastrointestinal cancers of epithelial origin worldwide, with over 2 million cases detected every year. Emerging evidence suggests a significant increase in the levels of inflammatory and stress‐related markers in patients with CRC, indicating that oxidative stress and lipid peroxidation may influence signalling cascades involved in the progression of the disease. However, the precise molecular and cellular basis underlying CRC and their modulations during bioactive compound exposure have not yet been deciphered. This study examines the effect of caffeic acid phenethyl ester (CAPE), a natural bioactive compound, in HT29 CRC cells grown under serum‐supplemented and serum‐deprived conditions. We found that CAPE inhibited cell cycle progression in the G2/M phase and induced apoptosis. Migration assay confirmed that CAPE repressed cancer invasiveness. Protein localisation by immunofluorescence microscopy and protein expression by western blot analysis reveal increased expressions of key inflammatory signalling mediators such as p38α, Jun N‐terminal kinase and extracellular signal‐regulated kinase (ERK) proteins. Molecular docking data demonstrates that CAPE shows a higher docking score of −5.35 versus −4.59 to known p38 inhibitor SB203580 as well as a docking score of −4.17 versus −3.86 to known ERK1/2 inhibitor AZD0364. Co‐immunoprecipitation data reveals that CAPE treatment effectively downregulates heat shock protein (HSP) expression in both sera‐supplemented and limited conditions through its interaction with mitogen‐activated protein kinase 14 (MAPK14). These results suggest that stress induction via serum starvation in HT29 CRC cells leads to the induction of apoptosis and co‐ordinated activation of MAPK‐HSP pathways. Molecular docking studies support that CAPE could serve as an effective inhibitor to target p38 and MAPK compared to their currently known inhibitors.

Publisher

Wiley

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