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http://dx.doi.org/10.4062/biomolther.2018.047

Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways  

Han, Xia (Jeju National University School of Medicine)
Kang, Kyoung Ah (Jeju National University School of Medicine)
Piao, Mei Jing (Jeju National University School of Medicine)
Zhen, Ao Xuan (Jeju National University School of Medicine)
Hyun, Yu Jae (Jeju National University School of Medicine)
Kim, Hyun Min (Jeju National University School of Medicine)
Ryu, Yea Seong (Jeju National University School of Medicine)
Hyun, Jin Won (Jeju National University School of Medicine)
Publication Information
Biomolecules & Therapeutics / v.27, no.1, 2019 , pp. 41-47 More about this Journal
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 $IC_{50}$ value of $3{\mu}M$ after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G_1$ 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 $PERK/elF2{\alpha}/CHOP$ apoptotic pathway, and mitochondrial $Ca^{2+}$ 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.
Keywords
Shikonin; Human colon cancer; Apoptosis; Mitochondria; Endoplasmic reticulum;
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