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KMID : 0606920220300020137
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Biomolecules & Therapeutics
2022 Volume.30 No. 2 p.137 ~ p.144
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Natural Compound Shikonin Induces Apoptosis and Attenuates Epithelial to Mesenchymal Transition in Radiation-Resistant Human Colon Cancer Cells
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Shilnikova Kristina
Piao Mei Jing
Kang Kyoung-Ah
Fernando Pincha Devage Sameera Madushan
Herath Herath Mudiyanselage Udari Lakmini
Cho Suk-Ju
Hyun Jin-Won
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Abstract
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Radiation resistance represents an imperative obstacle in the treatment of patients with colorectal cancer, which remains difficult to overcome. Here, we explored the anti-proliferative and migration-inhibiting properties of the natural product shikonin on a radiation-resistant human colon carcinoma cell line (SNU-C5RR). Shikonin reduced the viability of these cells in a dose-dependent manner; 38 μM of shikonin was determined as the half-maximal inhibitory concentration. Shikonin induced apoptotic cell death, as demonstrated by increased apoptotic body formation and the number of TUNEL-positive cells. Moreover, shikonin enhanced mitochondrial membrane depolarization and Bax expression and also decreased Bcl-2 expression with translocation of cytochrome c from mitochondria into the cytosol. In addition, shikonin activated mitogen-activated protein kinases, and their specific inhibitors reduced the cytotoxic effects of shikonin. Additionally, shikonin decreased the migration of SNU-C5RR cells via the upregulation of E-cadherin and downregulation of N-cadherin. Taken together, these results suggest that shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in SNU-C5RR cells.
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KEYWORD
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Shikonin, Radiation resistance, Human colon cancer, Epithelial to mesenchymal transition, Mitochondria-mediated apoptosis, Mitogen-activated protein kinases
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