Pyrrolizidine alkaloids from Liparis nervosa with antitumor activity by modulation of autophagy and apoptosis.

Abstract

Seven pyrrolizidine alkaloids, nervosine X-XV and nervosine VII N-oxide, together with a reaction product, namely chloride-(N-chloromethyl nervosine VII), were isolated from Liparis nervosa. Their structures were elucidated by extensive spectroscopic analyses. Most of these compounds were investigated for their cytotoxicity in vitro against HCT116 human cancer cell line, and the results showed that chloride-(N-chloromethyl nervosine VII) induced tumor cell death in a dose-dependent manner. Furthermore, the mechanisms underlying its cytotoxicity were investigated, including apoptosis and autophagy. Apoptosis in HCT116 cells was associated with up-regulation of caspase-3 and -9 expressions by activation of the mitochondrial pathway. The autophagy inducing effect was associated with the regulation of autophagic markers, including LC3-II, p62, and Beclin 1. Mechanistic studies showed that JNK, ERK1/2, and p38 MAPKs signaling cascades play an important role in chloride-(N-chloromethyl nervosine VII) induced autophagy and apoptosis.

• Authors: Lin Chen, Shuai Huang, Chun Ying Li, Feng Gao, Xian Li Zhou
• Journal: Phytochemistry (Phytochemistry) Vol. 153 Pg. 147-155 (Sep 2018) ISSN: 1873-3700 [Electronic] England
• PMID: 29980107 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Pyrrolizidine Alkaloids

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HCT116 Cells
• Humans
• Molecular Conformation
• Orchidaceae (chemistry)
• Pyrrolizidine Alkaloids (chemistry, isolation & purification, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured