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Shikonin induces apoptosis and G0/G1 phase arrest of gallbladder cancer cells via the JNK signaling pathway
Journal article   Open access   Peer reviewed

Shikonin induces apoptosis and G0/G1 phase arrest of gallbladder cancer cells via the JNK signaling pathway

Tianyu Zhai, Zhenyu Hei, Qiang Ma, Haibin Liang, Yi Xu, Yichi Zhang, Longyang Jin, Chao Han, Jiandong Wang and Hualou Liang
Oncology reports, v 38(6), pp 3473-3480
Dec 2017
PMID: 29039581
url
https://www.spandidos-publications.com/10.3892/or.2017.6038/downloadView
Published, Version of Record (VoR) Open
url
https://doi.org/10.3892/or.2017.6038View
Published, Version of Record (VoR) Open

Abstract

Animals Apoptosis - drug effects Caspases - genetics Cell Line, Tumor Cell Proliferation - drug effects G1 Phase Cell Cycle Checkpoints - drug effects Gallbladder Neoplasms - drug therapy Gallbladder Neoplasms - genetics Gallbladder Neoplasms - pathology Humans MAP Kinase Signaling System - drug effects Membrane Potential, Mitochondrial - drug effects Mice Naphthoquinones - administration & dosage Xenograft Model Antitumor Assays
Shikonin, a natural product isolated from the roots of Lithospermum erythrorhizon, is considered to have antitumor effects. Gallbladder cancer (GBC) is a prevalent biliary tract malignancy with few curative therapeutic stragegies and poor prognosis. In the present study, we detected the effects of shikonin on GBC cells as well as the underlying molecular mechanisms. The results demonstrated that GBC cell proliferation was inhibited by shikonin as determined by MTT and colony formation assays. Flow cytometry results demonstrated that shikonin treatment enhanced apoptosis and promoted G0/G1 phase arrest in the GBC cells. Western blot assay showed that shikonin induced mitochondrial-dependent apoptosis via the JNK signaling pathway. Moreover, shikonin suppressed tumor growth in mice bearing GBC-derived xenografts in a dose‑dependent manner without side-effects. These results revealed that shikonin exhibits anticancer effects on GBC cells by inducing apoptosis and regulating the cell cycle. Taken together, shikonin may be a novel and safe chemotherapeutic agent for the treatment of GBC.

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