Abstract
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer. We found that shikonin suppressed the growth of colon cancer cells in a dose-dependent manner in vitro and in vivo. Shikonin induced mitochondria-mediated apoptosis, which was regulated by Bcl-2 family proteins. Shikonin increased the generation of intracellular ROS, which played an upstream role in shikonin-induced apoptosis. Our data indicated that generation of ROS, down-regulated expression of Bcl-2 and Bcl-xL, depolarization of the mitochondrial membrane potential and activation of the caspase cascade were components of the programmed event of shikonin-induced apoptosis in colon cancer cells. In addition, shikonin presented minimal toxicity to non-neoplastic colon cells and no liver injury in xenograft models, showing safety in the control of colon cancer cell growth in vitro and in vivo. Taken together, our findings suggest that shikonin might serve as a potential novel therapeutic drug in the treatment of human colon cancer.
Highlights
Colon cancer is considered one of the most commonly diagnosed cancers worldwide
The toxicity of shikonin increased time-dependently, and the human normal colon mucosal epithelial cell line NCM460 was less sensitive to the increasing incubation time than the human colon cancer cell lines HCT116 and SW480
We found that shikonin suppressed the proliferation of colon cancer cells in a dose-dependent manner both in vitro and in vivo
Summary
Colon cancer is considered one of the most commonly diagnosed cancers worldwide. The incidence of colon cancer is high in developed countries, reflecting a prevalence of risk factors, including an unhealthy diet and obesity [1]. Surgical resection is mainly a curative therapy in the early stage, many patients are in an advanced stage at the time of diagnosis due to the lack of colon cancer screening [3, 4]. Chemotherapy is a commonly used strategy in colon cancer. Many patients eventually relapse and develop drug resistance [5, 6]. On this account, searching for novel drugs with efficacy and safety in the treatment of colon cancer is of utmost importance
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