2. Academic Validation
  3. Mitochondrial targeting derivatives of honokiol enhanced selective antitumor activity in NCI-H446 cells and decreased in vivo toxicity in Caenorhabditis elegans

Mitochondrial targeting derivatives of honokiol enhanced selective antitumor activity in NCI-H446 cells and decreased in vivo toxicity in Caenorhabditis elegans

  • Eur J Med Chem. 2023 Dec 3:264:115996. doi: 10.1016/j.ejmech.2023.115996.
Huicong Miao 1,  Wenbo Cui 1,  Tao Zhang 2,  Yue Zhang 1,  Jiaozhen Zhang 1,  Hongxiang Lou 3,  Peihong Fan 4
Affiliations

Affiliations

  • 1 Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
  • 2 Shandong Provincial Key Laboratory of Neuroprotective Drugs, Shandong Qidu Pharmaceutical Research Institute, Zibo 255400, PR China.
  • 3 Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China. Electronic address: louhongxiang@sdu.edu.cn.
  • 4 Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China. Electronic address: fanpeihong@sdu.edu.cn.
PMID: 38086195 DOI: 10.1016/j.ejmech.2023.115996
Abstract

Mitochondria, responsible for ATP production and Apoptosis regulation, play a key role in Cancer cells. Honokiol regulates Apoptosis through the endogenous mitochondrial pathway but does not specifically target tumor cells. We designed 28 novel derivatives of honokiol using triple-function delocalized lipophilic cations such as berberine and F16 as mitochondrion-targeting carriers. While all derivatives exhibited enhanced cytotoxicity toward tumor cells compared to honokiol, the derivative 2E-3-F16 exhibited a substantial tumor cell selectivity between NCI-H446 Cancer cells and HBE cells by one order of magnitude and enhanced the sensitivity of A549 cells to cisplatin. Mechanistically, it targeted mitochondria and induced Apoptosis by preventing tumor cells from entering the G0/G1 phases as well as inducing an abnormal elevation of Reactive Oxygen Species, thereby decreasing the mitochondrial membrane potential level. It also showed lower toxicity toward Caenorhabditis elegans than honokiol. This study provides a possible method for developing mitochondrion-targeting antitumor drugs with high efficiency and low toxicity based on Natural Products.

Keywords

Antitumor; DLCs; F16; Honokiol; Mitochondria targeting.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-157292
    Anticancer Agent