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Published on: July 17, 2018
Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer
Wenquan Liang1,2, Jianxin Cui1,2, Kecheng Zhang1,2
1Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
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.
Insights
Shikonin, a natural compound, effectively inhibits colon cancer growth by inducing apoptosis through reactive oxygen species (ROS) and mitochondrial pathways. It shows promise as a safe and effective colon cancer therapeutic agent.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Colon cancer is a leading global malignancy with significant recurrence rates due to chemotherapy resistance.
- Novel therapeutic strategies with improved efficacy and safety are critically needed for colon cancer treatment.
- Shikonin, a naphthoquinone from *Lithospermum erythrorhizon*, exhibits potent anti-tumor properties.
Purpose of the Study:
- To investigate the anti-tumor mechanisms of shikonin in colon cancer.
- To evaluate the efficacy and safety of shikonin as a potential colon cancer therapeutic.
Main Methods:
- In vitro and in vivo studies on colon cancer cell lines and xenograft models.
- Analysis of shikonin's effects on cell growth, apoptosis, reactive oxygen species (ROS) generation, and mitochondrial function.
- Assessment of Bcl-2 family protein expression, mitochondrial membrane potential, and caspase cascade activation.
Main Results:
- Shikonin suppressed colon cancer cell proliferation dose-dependently.
- Shikonin induced mitochondria-mediated apoptosis via ROS generation and Bcl-2 family protein regulation.
- Key events included ROS increase, Bcl-2/Bcl-xL downregulation, mitochondrial membrane potential depolarization, and caspase activation.
- Shikonin demonstrated minimal toxicity to normal colon cells and no liver injury in vivo.
Conclusions:
- Shikonin effectively induces apoptosis in colon cancer cells through ROS-mediated mitochondrial pathways.
- Shikonin exhibits a favorable safety profile, with low toxicity to non-cancerous cells and organs.
- Shikonin represents a promising novel therapeutic candidate for human colon cancer treatment.
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