Application of self-assembly peptides targeting the mitochondria as a novel treatment for sorafenib-resistant hepatocellular carcinoma cells.

Abstract

Currently, there is no appropriate treatment option for patients with sorafenib-resistant hepatocellular carcinoma (HCC). Meanwhile, pronounced anticancer activities of newly-developed mitochondria-accumulating self-assembly peptides (Mito-FF) have been demonstrated. This study intended to determine the anticancer effects of Mito-FF against sorafenib-resistant Huh7 (Huh7-R) cells. Compared to sorafenib, Mito-FF led to the generation of relatively higher amounts of mitochondrial reactive oxygen species (ROS) as well as the greater reduction in the expression of antioxidant enzymes (P < 0.05). Mito-FF was found to significantly promote cell apoptosis while inhibiting cell proliferation of Huh7-R cells. Mito-FF also reduces the expression of antioxidant enzymes while significantly increasing mitochondrial ROS in Huh7-R cells. The pro-apoptotic effect of Mito-FFs for Huh7-R cells is possibly caused by their up-regulation of mitochondrial ROS, which is caused by the destruction of the mitochondria of HCC cells.

• Authors: Tae Ho Hong, M T Jeena, Ok-Hee Kim, Kee-Hwan Kim, Ho Joong Choi, Kyung Hee Lee, Ha-Eun Hong, Ja-Hyoung Ryu, Say-June Kim
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 874 (01 13 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 33441650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organophosphorus Compounds
• Peptides
• Pyrenes
• Reactive Oxygen Species
• mito-FF
• tributylmethyl phosphonium chloride
• Phenylalanine
• pyrene
• Sorafenib

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems (methods)
• Drug Resistance, Neoplasm (drug effects, physiology)
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Mitochondria (metabolism)
• Organophosphorus Compounds (pharmacology, therapeutic use)
• Peptides (metabolism, pharmacology, therapeutic use)
• Phenylalanine (pharmacology, therapeutic use)
• Pyrenes (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Sorafenib (pharmacology)