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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1464626

Preparation and anti-colon cancer effect of a novel Curcumin Analogue (CA8): in Vivo and in Vitro evaluation

Provisionally accepted
Jie Wen Jie Wen 1*Lingmao Zhao Lingmao Zhao 2*Zhuohan Li Zhuohan Li 1*Chao Pi Chao Pi 1*Xianhu Feng Xianhu Feng 3*Peng Shi Peng Shi 1Hongru Yang Hongru Yang 4*Ligang Chen Ligang Chen 5Xiaodong Wang Xiaodong Wang 6*Furong Liu Furong Liu 6*Yumeng Wei Yumeng Wei 1*Ling Zhao Ling Zhao 1*
  • 1 Southwest Medical University, Luzhou, China
  • 2 Longmatan People's Hospital, Luzhou, Sichuan Province, China
  • 3 Nanchong Central Hospital, Nanchong, Sichuan Province, China
  • 4 The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
  • 5 Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
  • 6 Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China

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

    Chemotherapy remains the first choice of treatment for colon cancer despite the inevitable adverse effects. Curcumin (CU) possesses antitumor activity but has poor aqueous solubility, low bioavailability, and weak activity. To address this, nine novel monocarbonyl CU analogues were designed, synthesized, and evaluated in the present study. Among them, CA8 exhibited the highest water solubility, which was approximately 2.37×10 6 times that of CU. In addition, compared with CU, its cytotoxicity on Caco-2 cells (19.2 times/48 h) was stronger. Of note, CA8 arrestedthe cell cycle of Caco-2 cells at the G2/M phase and induced apoptosis. Meanwhile, acute toxicity experiments indicated that KM mice tolerated CA8 for up to 300 mg/kg CA8 (oral administration) and 50 mg/kg CA8 (intraperitoneal injection). The oral administration of CA8 to Sprague Dawley rats exhibited higher AUC (0-t) (6.23-fold) and longer MRT (0-t) (3.35-fold) than that of CU. CA8 also inhibited the proliferation and angiogenesis of tumor cells more than CU and tegafur. Finally, CA8 may exert antitumor effects through the activation of JNK pathway and inhibition of AKT pathway.These results suggest that CA8 is a safe and highly effective new drug for colon cancer treatment.

    Keywords: monocarbonyl CU analogues, Colon Cancer, Akt, JNK, Apoptosis

    Received: 14 Jul 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Wen, Zhao, Li, Pi, Feng, Shi, Yang, Chen, Wang, Liu, Wei and Zhao. 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:
    Jie Wen, Southwest Medical University, Luzhou, China
    Lingmao Zhao, Longmatan People's Hospital, Luzhou, Sichuan Province, China
    Zhuohan Li, Southwest Medical University, Luzhou, China
    Chao Pi, Southwest Medical University, Luzhou, China
    Xianhu Feng, Nanchong Central Hospital, Nanchong, 637000, Sichuan Province, China
    Hongru Yang, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
    Xiaodong Wang, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
    Furong Liu, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
    Yumeng Wei, Southwest Medical University, Luzhou, China
    Ling Zhao, Southwest Medical University, Luzhou, 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.