Biomol Ther.  2022 Mar;30(2):137-144. 10.4062/biomolther.2021.088.

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

• Shilnikova K
• Piao MJ
• Kang KA
• Madushan Fernando PDS
• Lakmini Herath HMU
• Cho SJ
• Hyun JW

• KMID: 2526815
• DOI: http://doi.org/10.4062/biomolther.2021.088

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.

Keyword

Shikonin; Radiation resistance; Human colon cancer; Epithelial to mesenchymal transition; Mitochondria-mediated apoptosis; Mitogen-activated protein kinases