Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line.

Mohammed Nihal Hasan,Tadao Asami,Christian Bronner,Mazin A Zamzami,Hani Choudhry,Abdulrahman Labeed Al-Malki,Jiannis Ragoussis,Mahmoud Alhosin,Wei Wu,Taha Abduallah Kumosani,Majed A Halwani,Khalid Omer Abualnaja,Syed Shoeb Razvi,Said Salama Moselhy,Mohammed A Hassan

doi:10.1155/2019/1598182

Abstract

Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.

Highlights

In 2012, 0.8 million patients were diagnosed with liver cancer, the seventh highest age-related incidence rate globally [1]
Data obtained from HepG2 cells treated with 60 μM of SL analogue of TIT3 revealed that the mRNA expression of 3240 genes was modulated, with 1473 genes being upregulated and 1767 genes being downregulated
The gene enrichment analysis of gene ontology (GO) terms (p < 0 0001) revealed that there was a significant increase in the negative regulation of transcription by the RNA polymerase II promoter and negative regulation of G1/S transition of mitosis and a substantial decrease in the damaged DNA repair genes

Summary

Introduction

In 2012, 0.8 million patients were diagnosed with liver cancer, the seventh highest age-related incidence rate globally [1]. HCC is the third most common cancer-related cause of mortality globally [1]. There exists an inveterate history of compounds, derived from plants, serving as anticancer agents [4]. These compounds can exert their inhibitory effects on cancer cells by targeting several pathways including cell cycle arrest, cell proliferation, and apoptosis. It has previously been reported that synthetic SL analogues instigate G2/M cell cycle arrest and apoptosis by regulating the p38 and JNK1/2 MAPKs signaling pathways, causing the induction of stress in an array of solid and nonsolid human cancer cells, including prostate, colon, leukemia, osteosarcoma, and lung cancer cell lines

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Results

Conclusion