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Int J Med Sci 2022; 19(12):1806-1815. doi:10.7150/ijms.72987 This issue Cite

Research Paper

Molecular Changes Following Induction of Hepatocellular Carcinoma by Diethylnitrosamine and Thioacetamide, and Subsequent Treatment with Dioscorea membranacea Extract

Vichununt Kerdput¹, Kritsakorn Kanjanapongkul², Arunporn Itharat³, Ratchadaporn Pramong¹, Wouter H Lamers⁴, Theodorus B. M. Hakvoort⁴, Aldo Jongejan⁵, Wisuit Pradidarcheep^1✉

1. Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
2. Department of Science, Mahidol University International College, Mahidol University, Nakhon Pathom 73170, Thailand.
3. Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathumthani 10120, Thailand.
4. Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location AMC, 1105 BK Amsterdam, The Netherlands.
5. Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

✉ Corresponding author: Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, 23 Sukhumvit Road, Bangkok 10110, Thailand. E-mail address: wisuitswu.ac.th (W. Pradidarcheep). Phone number: +6622601532.

Abstract

Hepatocellular carcinoma (HCC) is a primary liver cancer commonly found in adults. Previously, we showed the anticancer effects of Thai herbal plant extract, Dioscorea membranacea Pierre (DM), in HCC-bearing rats. In the present study, we further examined the proposed mechanism of DM, including apoptosis and antioxidant activity. Moreover, we used RNA sequencing (RNA-seq) to analyze molecular pathways in the rat model in which HCC was induced by diethylnitrosamine (DEN) and thioacetamide (TAA). The HCC-bearing rats were then treated with 40 mg/kg of DM for 8 weeks, after which experimental and control rats were sacrificed and liver tissues were collected. The RNA-seq data of DEN/TAA-treated rats exhibited upregulation of 16 hallmark pathways, including epithelial mesenchymal transition, inflammatory responses, and angiogenesis (p<0.01). DM extract expanded the Bax protein-positive pericentral zone in the tumor areas and decreased hepatic malondialdehyde levels, implying a decrease in lipid peroxidation in liver. However, DM treatment did not ameliorate the molecular pathways induced in DEN/TAA-treated livers. Our findings indicate that DM extract has antioxidant activity and exerts its pro-apoptotic effect on rat HCCs in vivo at the (post-)translational level.

Keywords: Dioscorea membranacea, liver cancer, apoptosis, malondialdehyde, RNA sequencing

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