Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways

Jing,Huiling; Sun,Wenyan; Fan,Jinghua; Zhang,Yanmin; Yang,Jiao; Jia,Jinjing; Li,Jichang; Guo,Jiaqi; Luo,Suju; Zheng,Yan

doi:10.3892/mmr.2016.4917

Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways

Authors:
- Huiling Jing
- Wenyan Sun
- Jinghua Fan
- Yanmin Zhang
- Jiao Yang
- Jinjing Jia
- Jichang Li
- Jiaqi Guo
- Suju Luo
- Yan Zheng
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Affiliations: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Physiology and Pathophysiology, Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Dermatology, Tianjin Medical University General Hospital, Tianjin 300070, P.R. China
Published online on: February 19, 2016 https://doi.org/10.3892/mmr.2016.4917
Pages: 3009-3016
Copyright: © Jing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Shikonin, which is a major ingredient of the traditional Chinese herb Lithospermum erythrorhizon, possesses various biological functions, including antimicrobial, anti-inflammatory, and antitumor activities. The present study aimed to determine the molecular mechanisms underlying the effects of shikonin on HaCaT cell apoptosis. Treatment with shikonin significantly inhibited the viability of HaCaT cells in a dose‑ and time‑dependent manner, and promoted cell cycle arrest at G0/G1 phase and apoptosis. In addition, shikonin treatment reduced the mitochondrial membrane potential and induced reactive oxygen species generation. The results of a western blot analysis demonstrated that shikonin significantly activated caspase 3 expression, downregulated B‑cell lymphoma 2 (Bcl‑2) expression, and upregulated Bcl‑2‑associated X protein and Bcl‑2 homologous antagonist killer expression in a dose‑dependent manner in HaCaT cells. Furthermore, shikonin decreased extracellular signal‑regulated kinase (Erk) and Akt phosphorylation. These results indicated that shikonin may exert its anti‑proliferative effects by inducing apoptosis via activation of the mitochondrial signaling pathway and inactivation of the Akt and Erk pathways in HaCaT cells. Therefore, the present study suggested that shikonin may have potential as a component of therapeutic strategies for the treatment of skin diseases.

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