2. Academic Validation
  3. Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells

Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells

  • Biomed Pharmacother. 2021 May:137:111335. doi: 10.1016/j.biopha.2021.111335.
Yulai You 1,  Fengfeng Zhu 2,  Zhenhuan Li 3,  LingFeng Zhang 4,  Yu Xie 5,  Arunachalam Chinnathambi 6,  Tahani Awad Alahmadi 7,  Bei Lu 8
Affiliations

Affiliations

  • 1 Department of Liver and Gallbladder Surgery, Jiangjin District Central Hospital of Chongqing, Chongqing, 402260, China.
  • 2 Department of Hepatobiliary Surgery, the First Affiliated Hospital of University of South China, Hengyang, Hunan, 421001, China.
  • 3 Department of General Surgery, Xi'an NO.5 Hospital, Xi'an City, Shaanxi Province, 710082, China.
  • 4 Department of Hepatobiliary Surgery, The First People's Hospital of Huaihua City, Huaihua, Hunan, 418000, China.
  • 5 Department of Liver and Gallbladder Surgery, the PLA Rocket Force General Hospital, Beijing, 100088, China.
  • 6 Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
  • 7 Department of Pediatrics, College of Medicine, King Saud University, [Medical City], King Khalid University Hospital, PO Box-2925, Riyadh, 11461, Saudi Arabia.
  • 8 Department of Hepato-pancreato-biliary Surgery, Affiliated Hangzhou First People's Hospital，Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China. Electronic address: lubei_2019@sina.com.
PMID: 33581648 DOI: 10.1016/j.biopha.2021.111335
Abstract

Liver Cancer is a critical clinical condition with augmented malignancy, rapid progression, and poor prognosis. Liver Cancer often initiates as fibrosis, develops as cirrhosis, and results in Cancer. For centuries, medicinal Plants have been incorporated in various liver-associated complications, and recently, research has recognized that many bioactive compounds from medicinal Plants may interact with targets related to liver disorders. Phyllanthin from the Phyllanthus species is one such compound extensively used by folklore practitioners for various health benefits. However, most practices continue to be unrecognized scientifically. Hence, in this work, we investigated the protective role of phyllanthin on diethylnitrosamine (DEN) induced liver carcinoma in Wistar Albino rats and the anti-tumor potential on human hepatocellular carcinoma (HCC) HepG2 cells. The DEN-challenged liver Cancer in experimental rats caused increased liver weight, 8-OHD, hepatic tissue injury marker, lipid peroxidation, and tumor markers levels. Remarkably, phyllanthin counteracted the DEN effect by ameliorating all the liver function Enzymes, oxidative DNA damage, and tumor-specific markers by enhanced anti-oxidant capacity and induced caspase-dependent Apoptosis through the mTOR/ PI3K signaling pathway. MTT assay demonstrated that phyllanthin inhibited the HepG2 cell growth in a dose-dependent manner. Fascinatingly, phyllanthin did not demonstrate any substantial effect on the normal cell line, HL7702. In addition, HepG2 cells were found in the late apoptotic stage upon treatment with phyllanthin as depicted by acridine orange/ethidium bromide staining. Overall, this work offers scientific justification that phyllanthin can be claimed to be a safe candidate with potential chemotherapeutic activity against HCC.

Keywords

Diethylnitrosamine; HepG2 cell line; Hepatocellular carcinoma; Phyllanthin; mTOR/PI3K signaling pathway.

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