Abstract
Colorectal cancer is a common malignancy occurring in the digestive system, which is the third common cause of cancer mortality in developed countries. Shikonin, a naphthoquinone compound extracted from the root of Lithospermum erythrorhizon, is extensively reported to exert antitumor activity against various types of cancer. However, the systematic effect of shikonin in colon cancer remains poorly understood. In the present study, we evaluated the antitumor activity of shikonin in human colon cancer cells and the therapeutic effect on a xenograft mouse model. Transcriptomics and metabolomics were further integrated to provide a systematic perspective of the shikonin-induced antitumor mechanism. The results demonstrated that shikonin had a remarkable antitumor potency both in vitro and in vivo. Moreover, metabolic pathways, including the purine metabolism, amino acid metabolism, and glycerophospholipid metabolism, were perturbed and subsequently led to cell cycle arrest in the G2/M phase. In particular, the disturbance of purine metabolism may account for the major mechanism resulting from shikonin antitumor activity.
Highlights
Colorectal cancer (CRC) is a common malignancy occurring in the digestive system, and it is reported as the fourth major cause for cancer-related mortality in the world (Gansler et al, 2010)
The cytotoxicity of different concentrations of shikonin was exhibited in four human colon cancer cell lines HT29, HCT116, SW620, and SW480 (Figures 1A–D), which suggested that the significant cytotoxicity exerted by shikonin was in a dose-dependent manner
13 differential metabolites involved in the purine metabolism were significantly regulated under the treatment of shikonin, which accounted for the highest impact among the perturbed pathways
Summary
Colorectal cancer (CRC) is a common malignancy occurring in the digestive system, and it is reported as the fourth major cause for cancer-related mortality in the world (Gansler et al, 2010). Surgical resection combined with chemotherapy and radiotherapy is still served as the predominant treatment for early- and mid-stage patients with localized colon cancer. Their side effects are considerable, and the poor prognosis is valued to be addressed (Schlick et al, 2019). The development of natural products has become a priority for the therapy of colorectal cancer. A diversity of antitumor mechanisms involved in shikonin has been reported, including inhibiting cell proliferation (Huang and Hu, 2018), inducing apoptosis (Zhai et al, 2017), and activating necroptosis (Shahsavari et al, 2018).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
