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http://dx.doi.org/10.4062/biomolther.2021.088

Natural Compound Shikonin Induces Apoptosis and Attenuates Epithelial to Mesenchymal Transition in Radiation-Resistant Human Colon Cancer Cells  

Shilnikova, Kristina (College of Medicine, Jeju National University)
Piao, Mei Jing (College of Medicine, Jeju National University)
Kang, Kyoung Ah (College of Medicine, Jeju National University)
Fernando, Pincha Devage Sameera Madushan (College of Medicine, Jeju National University)
Herath, Herath Mudiyanselage Udari Lakmini (College of Medicine, Jeju National University)
Cho, Suk Ju (College of Medicine, Jeju National University)
Hyun, Jin Won (College of Medicine, Jeju National University)
Publication Information
Biomolecules & Therapeutics / v.30, no.2, 2022 , pp. 137-144 More about this Journal
Abstract
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.
Keywords
Shikonin; Radiation resistance; Human colon cancer; Epithelial to mesenchymal transition; Mitochondria-mediated apoptosis; Mitogen-activated protein kinases;
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