Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways.
10.4062/biomolther.2018.047
- Author:
Xia HAN
1
;
Kyoung Ah KANG
;
Mei Jing PIAO
;
Ao Xuan ZHEN
;
Yu Jae HYUN
;
Hyun Min KIM
;
Yea Seong RYU
;
Jin Won HYUN
Author Information
1. Jeju National University School of Medicine, Jeju 63243, Republic of Korea. jinwonh@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
Shikonin;
Human colon cancer;
Apoptosis;
Mitochondria;
Endoplasmic reticulum
- MeSH:
Apoptosis;
bcl-2-Associated X Protein;
Caspase 9;
Cell Death*;
Cell Line;
Colon*;
Colonic Neoplasms*;
DNA Fragmentation;
Endoplasmic Reticulum*;
Extracellular Vesicles;
Humans*;
Inhibitory Concentration 50;
Lymphoma, B-Cell;
Mitochondria;
Mitochondrial Membranes;
Protein Kinases
- From:Biomolecules & Therapeutics
2019;27(1):41-47
- CountryRepublic of Korea
- Language:English
-
Abstract:
The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated IC50 value of 3 µM after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G1 phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/CHOP apoptotic pathway, and mitochondrial Ca2+ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER-and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.
