TY - JOUR
T1 - Molecular Changes Following Induction of Hepatocellular Carcinoma by Diethylnitrosamine and Thioacetamide, and Subsequent Treatment with Dioscorea membranacea Extract
AU - Kerdput, Vichununt
AU - Kanjanapongkul, Kritsakorn
AU - Itharat, Arunporn
AU - Pramong, Ratchadaporn
AU - Lamers, Wouter H.
AU - Hakvoort, Theodorus B. M.
AU - Jongejan, Aldo
AU - Pradidarcheep, Wisuit
N1 - Funding Information: This work was supported by grants from Thailand Science Research and Innovation Fund [grant number 014/2564], Faculty of Medicine, Srinakharinwirot University, Thailand [grant number 143/2565], and the Royal Golden Jubilee Ph.D. Program [grant number PHD/0037/2557]. Publisher Copyright: © The author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Dioscorea membranacea
KW - RNA sequencing
KW - apoptosis
KW - liver cancer
KW - malondialdehyde
UR - http://www.scopus.com/inward/record.url?scp=85140132759&partnerID=8YFLogxK
U2 - https://doi.org/10.7150/ijms.72987
DO - https://doi.org/10.7150/ijms.72987
M3 - Article
C2 - 36313224
SN - 1449-1907
VL - 19
SP - 1806
EP - 1815
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
IS - 12
ER -