Extract of Saccharina japonica induces apoptosis companied by cell cycle arrest and endoplasmic reticulum stress in SK-Hep1 human hepatocellular carcinoma cells.

Hyun Il Jung,Gun-Do Kim,Hyung-Rak Kim,Yung Hyun Choi,Mi Jeong Jo

doi:10.7314/apjcp.2014.15.7.2993

Abstract

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

Highlights

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally, behind lung and stomach cancers and is increasing more than 626,000 new cases per year in the world (Rebecca et al, 2013)
The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells
We evaluated the potential anti-cancer activities of S. japonica n-hexane extract in an aspect of apoptosis companied by cell cycle arrest and induction of endoplasmic reticulum (ER)-stress in SK-Hep1 hepatocellular carcinoma cells

Summary

Introduction

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally, behind lung and stomach cancers and is increasing more than 626,000 new cases per year in the world (Rebecca et al, 2013). To combat the deleterious effects of ER-stress, cells have evolved various protective strategies, collectively termed the unfolded protein response (UPR). This concerted and complex cellular response is mediated through three ER transmembrane receptors: pancreatic ER kinase (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1) (Oyadomari et al, 2002; Wang et al, 2014). We evaluated the potential anti-cancer activities of S. japonica n-hexane extract in an aspect of apoptosis companied by cell cycle arrest and induction of ER-stress in SK-Hep hepatocellular carcinoma cells

Materials and Methods

Results

Discussion