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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1360587
This article is part of the Research Topic Discovery of Small Molecule Lead Compounds: a Driving Force to Unravel New Anti-Cancer Targets and Mechanisms - Volume II View all 6 articles

Systematic Bioinformatics Analysis Reveals the Role of Shikonin in Blocking Colon Cancer Progression by Identifying Senescence-Induced Genes

Provisionally accepted
Wenna Liu Wenna Liu 1Yujia Zhao Yujia Zhao 2Qingqing Liu Qingqing Liu 1Dan Wu Dan Wu 1Wenxuan Li Wenxuan Li 3Zhenkai Fu Zhenkai Fu 4Le Yang Le Yang 1Ying Liang Ying Liang 5*
  • 1 Air Force Medical University, Xi'an, Shaanxi Province, China
  • 2 Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
  • 3 Fudan University, Shanghai, Shanghai Municipality, China
  • 4 Peking University, Beijing, Beijing Municipality, China
  • 5 Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Air Force Medical University, Xi'an, China

The final, formatted version of the article will be published soon.

    Shikonin, a naturally occurring naphthoquinone compound extracted from comfrey plants, has antitumor, anti-inflammatory, and antimicrobial properties. Cell senescence plays a key role in preventing tumor progression. It is unclear whether shikonin has an effect on cell senescence in colon cancer. In the current study, we firstly determine the IC50 values of shikonin on colon cancer cell lines HT29 and HCT116, respectivelywere cultured with different concentrations of shikonin (0 μM, 6 μM, 12 μM, 24 μM, and 48 μM for HT29 cells, and 0 μM, 0.3 μM, 0.9 μM, 2.7 μM, and 8.1 μM for HCT116 cells) for 24 h. Then, wWe verified the inhibitory effects of shikonin on the proliferation and migration abilities of colon cancer cell lines HT29 and HCT116 using cell proliferationcounting kit-8, colony formation, and wound healing assays. Next, we identified a series of potential targets using highthroughput mRNA sequencing, and identified 210 upregulated and 296 downregulated genes. KEGG profiling revealed that eight downregulated genes associated with cell senescence: CCNB3, IL-1α, CXCL8, CDKN2A, MYC, IGFBP3, SQSTM1 and GADD45G. CXCL8 and CDKN2A were associated with poor prognosis in patients with colon cancer, suggesting that their downregulation by shikonin could improve patient survival. Furthermore, SA-β-galactosidase staining revealed that the percentage of cellular senescence in colon cancer cells was significantly increased after shikonin treatment. Molecular docking revealed that shikonin suppressed colon cancer progression by blocking CXCL8 activity. Based on these findings, we deem that Sshikonin might induce senescence and exert antitumor activity in colon cancer cells by downregulating CDKN2A and CXCL8. This provides a new molecular mechanism and potential therapeutic target for shikonin to inhibit colon cancer progression.

    Keywords: Shikonin, cell senescence, bioinformatics, antitumor, molecular docking

    Received: 23 Dec 2023; Accepted: 26 Jul 2024.

    Copyright: © 2024 Liu, Zhao, Liu, Wu, Li, Fu, Yang and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ying Liang, Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Air Force Medical University, Xi'an, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.