Targeting the Hippo and Rap1 signaling pathways: the anti-proliferative effects of curcumin in colorectal cancer cell lines

Abstract

CRC has the third-highest cancer incidence and death. Many human cancers, including colorectal cancer, are connected to abnormal signaling pathway gene expression. Many human malignancies include Hippo and Rap1 signaling. This research examined curcumin's therapeutic effects on colorectal cancer cell lines' Hippo and Rap1 signaling pathway genes. The role of the above signaling pathways is considered in colorectal cancer development. No research has examined curcumin's influence on key genes in these pathways; thus, this work is meant to uncover its more precise mechanism. First, the gene expression omnibus database is queried to discover GSE8671, a dataset that contains differentially expressed genes associated in CRC formation. DAVID was used to discover the corporation of these genes and signaling pathways (Hippo and Rap1), and the cancer genome atlas (TCGA) database was utilized to select genes and assess their expression and biomarker potential. MTT, apoptosis, and quantitative PCR were used to assess whether curcumin is therapeutic for colorectal cancer cell lines. An in-silico analysis identified the dysregulation of several critical genes AXIN2, MYC, TEAD4, MET, LPAR1, and ADCY9 in colorectal cancer, highlighting their involvement in the Hippo and Rap1 signaling pathways. Experimental assessments, including MTT assays, apoptosis assays, and quantitative PCR (qPCR) analysis, demonstrated that the targeted modulation of these genes effectively inhibits cancer cell proliferation. Specifically, treatment with curcumin resulted in a significant reduction in cell viability in HT-29 and HCT-116 colorectal cancer cell lines, thereby facilitating apoptotic cell death. Furthermore, curcumin administration was associated with the upregulation of LPAR1 and ADCY9 gene expression, while concurrently downregulating AXIN2, MYC, TEAD4, and MET in both cell lines. This study reveals compelling evidence of curcumin's potent anticancer properties, highlighting its transformative influence on the Hippo and Rap1 signaling pathways within colorectal cancer cells. These findings not only underscore curcumin's potential as a therapeutic agent but also pave the way for innovative strategies in the fight against colorectal cancer.

Keywords: Colorectal cancer; Computational biology; Curcumin; Hippo; Rap1; Systems biology.