JI-CS004, a chloroform fraction of SH003, induces reactive oxygen species-dependent intrinsic apoptosis via endoplasmic reticulum stress-associated mitochondrial dysfunction in human colorectal cancer cells.

Authors

Tae-Hyoun Kim, Kwang-Jin Cho, Hyun-Ha Hwang, Hyeong-Chan Lee, Seong-Gyu Ko

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Conventional therapies for colorectal cancer (CRC) are often limited by toxicity and therapeutic resistance. Alternative therapeutic strategies are therefore needed. Natural product-derived compounds have been explored as potential anticancer agents. The molecular mechanisms underlying the anticancer effects of JI-CS004, a chloroform fraction derived from the herbal formulation SH003, against CRC remain unclear.
The anticancer effects of JI-CS004 were evaluated in CRC cell lines by assessing reactive oxygen species (ROS) generation, ER stress signaling, mitochondrial dysfunction, and intrinsic apoptosis. ROS dependency was examined using N-acetylcysteine (NAC). Antitumor activity was evaluated in an HCT116 xenograft model.
JI-CS004 substantially reduced CRC cell viability and induced intracellular ROS accumulation. ROS scavenging by NAC markedly attenuated JI-CS004-induced cytotoxicity, ER stress signaling, mitochondrial dysfunction, and intrinsic apoptosis, supporting an important contribution of ROS to these cellular responses. JI-CS004 activated ER stress-related signaling through the PERK/eIF2α/ATF4 and IRE1α/JNK pathways, increased CHOP expression, reduced mitochondrial membrane potential and OXPHOS complex expression, and induced intrinsic apoptosis accompanied by cytochrome c release and caspase-9/3 activation. In vivo, JI-CS004 substantially suppressed tumor growth and increased the expression of CHOP and cleaved caspase-3.
JI-CS004 induces ROS-dependent intrinsic apoptosis associated with ER stress and mitochondrial dysfunction, supporting further investigation of its anticancer potential in CRC.

PMID:
42627401
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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