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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Gastrointestinal and Hepatic Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1552486

Inhibition of colorectal cancer cell growth by down-regulation of M2-PK and reduction of aerobic glycolysis by clove active ingredients

Provisionally accepted
Lin Liu Lin Liu 1Gang Xing Gang Xing 1Xiaoyi Guo Xiaoyi Guo 1Hui Chen Hui Chen 1Jian Li Jian Li 2Jian Wang Jian Wang 3Yaling Li Yaling Li 4Gang Liang Gang Liang 2Minghua Liu Minghua Liu 1*
  • 1 Southwest Medical University, Luzhou, Sichuan, China
  • 2 Pharmacy Department, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
  • 3 Discipline Construction Office, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
  • 4 The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China

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

    Exploring the anti-tumour molecular mechanisms of traditional Chinese medicines has become an important strategy to develop novel anti-tumour drugs to the clinic. Several pharmacological studies have reported the antioxidant, antibacterial, anti-inflammatory and anti-tumour effects of clove. Previously we have shown that the active fraction from clove (AFC) can inhibit the growth of tumor cells, particularly colon cancer cells, in vitro.However, the mechanism of action regarding the anti-colon cancer activity of AFC, especially in aerobic glycolysis, has not been adequately investigated. In this study, we found that AFC significantly inhibited the growth of five types of colon cancer cells and down-regulated the mRNA and protein levels of M2-type pyruvate kinase (PKM2), as well as reduced aerobic glycolysis capacity. Transfection of PKM2-siRNA mimicked the inhibitory effect of AFC on aerobic glycolysis in colon cancer cells. Furthermore, tumourspecific highly expressed targets c-myc and cyclin D1 in cells were also found to be downregulated following the action of AFC. In the HCT116 cell xenograft nude mice models, the results after AFC administration were consistent with the cellular experiments, while AFC caused less liver injury and weight loss than the conventional chemotherapeutic agent 5-FU. In conclusion, AFC inhibits colon cancer growth by downregulating PKM2 to inhibit aerobic glycolysis and reduces tumour-specific high expression of c-myc and cyclin D1.Future work should explore how it downregulates pyruvate kinase in the first place, and the intrinsic mechanism between the down-regulation of PKM2 and the down-regulation of cmyc.Keywords:active fraction from clove, M2-type pyruvate kinase, Aerobic glycolysis, Anti-colon cancer,cyclin D1.

    Keywords: active fraction from clove, M2-type pyruvate kinase, aerobic glycolysis, Anti-colon cancer, Cyclin D1

    Received: 28 Dec 2024; Accepted: 24 Mar 2025.

    Copyright: © 2025 Liu, Xing, Guo, Chen, Li, Wang, Li, Liang and Liu. 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: Minghua Liu, Southwest Medical University, Luzhou, Sichuan, 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.

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