Phenylpropanoid-conjugated pentacyclic triterpenoids from the whole plants of Leptopus lolonum induced cell apoptosis via MAPK and Akt pathways in human hepatocellular carcinoma cells.

Abstract

Our present and previous phytochemical investigations on Leptopus lolonum have resulted in the isolation of almost 30 phenylpropanoid-conjugated pentacyclic triterpenoids (PCPTs). During the continuous study on PCPTs, this kind of triterpenoid ester is considered as a natural product with low toxicity because of it's widely distribution in natural plants and edible fruits including kiwi fruit, durian, jujube, pawpaw, apple and pear. In the present work, we report the isolation, structural elucidation and cytotoxic evaluation of four new PCPTs (1-4) which obtained from L. lolonum. In addition, the possible biosynthesis pathway for 28-norlupane triterpenoid and potent effect of phenylpropanoid moiety for increasing the cytotxic effect of triterpenoids were also discussed. Among these compounds, compound 1 exhibited the highest cytotoxic effect on HepG2 cells with IC50 value of 11.87 μM. Further flow cytometry and western blot analysis demonstrated that 1 caused G1 cell cycle arrest by up-regulated the expression of phosphorylated p53 protein in HepG2 cells and induced cell apoptosis via MAPK and Akt pathways. These results emphasized the potential of PCPTs as lead compounds for developing anti-cancer drugs.

• Authors: Shi-Zhou Qi, Xin-Xin Zhang, Yue Jin, Miao Wang, Li-Ping Long, Wen-Hua Jing, Kai-Ru Song, Da Wang, Hui-Yuan Gao
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 111 Pg. 104886 (06 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 33836342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Plant Extracts
• Propanols
• Triterpenes
• Proto-Oncogene Proteins c-akt

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• MAP Kinase Signaling System (drug effects)
• Malpighiales (chemistry)
• Molecular Structure
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Plants, Medicinal (chemistry)
• Propanols (chemistry, isolation & purification, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Structure-Activity Relationship
• Triterpenes (chemistry, isolation & purification, pharmacology)