Lauric acid induce cell death in colon cancer cells mediated by the epidermal growth factor receptor downregulation.

Lauric acid induce cell death in colon cancer cells mediated by the epidermal growth factor receptor downregulation: An in silico and in vitro study.

Devi Lekshmi Sheela, Arunaksharan Narayanankutty, Pa Nazeem, A C Raghavamenon, S R Muthangaparambil

Hum Exp Toxicol

Apr 2, 2019

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Abstract

Coconut oil (CO) is enriched with medium chain saturated fatty acids like lauric acid (LA), capric acid and caprylic acid, which are known to have several health benefits. LA, the predominant fatty acid in CO, is reported to possess anticancer activity mediated through oxidative stress-induced apoptosis; however, there is no clear information on its cellular signalling mechanism. The present study screened the anticancer potential of various fatty acids present in CO (capric acid, caprylic acid and LA) using in silico tools such as CDOCKER in Accelrys Discovery Studio by targeting proteins like epidermal growth factor receptor (EGFR), cyclin-dependent kinase and thymidine synthase (TS). The results were further confirmed using cell culture-based studies and quantitative PCR. Among the tested compounds, LA was found to be the most active and showed a higher affinity towards EGFR and TS. Corroborating with these results, LA-induced dose-dependent cytotoxicity towards HCT-15 (human colon cancer), HepG2 (human hepatocellular carcinoma) and Raw 264.7 (murine macrophages) cells exhibiting morphological characteristics of apoptosis. Further, in HCT-15 cells exposed to LA (30 and 50µg/mL), the expression of EGFR was found to be downregulated by 1.33- and 1.58-fold. The study thus concludes that the anticancer activity of LA may be partially mediated by the downregulation of EGFR signalling and consequent reduction in cell viability through apoptosis. Since EGFR signalling iscrucial in cancer cell survival and is a prime target in drug development, the present study has pharmacological significance.