open access publication

Article, Early Access, 2024

Ancient forest plants possess cytotoxic properties causing liver cancer HepG2 cell apoptosis

ENVIRONMENTAL RESEARCH, ISSN 0013-9351, 0013-9351, Volume 241, 10.1016/j.envres.2023.117474

Contributors

Yue, Xiao 0000-0003-0438-2918 [1] Ling, Nyuk 0000-0002-1301-4730 [2] [3] Zhong, Jiateng [4] Yang, Han [1] Chen, Hui-Ling 0000-0003-4709-0851 [1] Yang, Yafeng 0000-0003-1064-2982 [1] Lam, Su Shiung 0000-0002-5318-1760 [3] [5] Yan, Lijun [1] Styrishave, B. 0000-0003-1619-2468 [6] Ciesielski, Tomasz Maciej [7] [8] Peng, Wan-Xi 0000-0002-3793-6588 (Corresponding author) [1] Sonne, Christian 0000-0001-5723-5263 (Corresponding author) [1] [9] [10]

Affiliations

  1. [1] Henan Agr Univ, Forestry Coll, Henan Prov Engn Res Ctr Biomass Value Added Prod, Zhengzhou 450002, Peoples R China
  2. [NORA names: China; Asia, East];
  3. [2] Saveetha Inst Med & Tech Sci SIMATS, Ctr Global Hlth Res CGHR, Chennai, India
  4. [NORA names: India; Asia, South];
  5. [3] Univ Malaysia Terengganu, Fac Sci & Marine Environm, BIOSES Res Interest Grp, Kuala Nerus 21030, Terengganu, Malaysia
  6. [NORA names: Malaysia; Asia, South];
  7. [4] Xinxiang Med Univ, Dept Pathol, Xinxiang, Peoples R China
  8. [NORA names: China; Asia, East];
  9. [5] Yuan Ze Univ, Dept Chem Engn & Mat Sci, Taoyuan, Taiwan
  10. [NORA names: Taiwan; Asia, East];

Abstract

Here, we collected 154 plant species in China ancient forests looking for novel efficient bioactive compounds for cancer treatments. We found 600 bioactive phyto-chemicals that induce apoptosis of liver cancer cell in vitro. First, we screen the plant extract's in vitro cytotoxicity inhibition of cancer cell growth using in vitro HepG2 cell lines and MTT cytotoxicity. The results from these initial MTT in vitro cytotoxicity tests show that the most efficient plants towards hepatoma cytoxicity is Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus). We then used in cell-counting kit-8 (CCK-8) to further understand in vivo tumor growth using nude mice and GC-MS and LC-QTOF-MS to analyze the composition of compounds in the extracts. Extracted chemically active molecules analyzed by network pharmacology showed inhibition on the growth of liver cancer cells by acting on multiple gene targets, which is different from the currently used traditional drugs acting on only one target of liver cancer cells. Extracts from Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus) induce apoptosis in hepatoma cancer cell line HepG2 with a killing rate of more than 83% and a tumor size decrease by 62-67% and a killing rate of only 6% of normal hepatocyte LO2. This study highlight efficient candidate species for cancer treatment providing a basis for future devel-opment of novel plant-based drugs to help meeting several of the UN SDGs and planetary health.

Keywords

Denmark, Forest, Genes, Planetary health, Treatment, UN SDGs

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