Garcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway

Abstract

<p>Despite various therapeutic approaches, <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/colorectal-cancer" title="Learn more about colorectal cancer from ScienceDirect's AI-generated Topic Pages">colorectal cancer</a> is among the most fatal <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/disease" title="Learn more about diseases from ScienceDirect's AI-generated Topic Pages">diseases</a> globally. Hence, developing novel and more effective methods for colorectal cancer <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/therapeutic-procedure" title="Learn more about treatment from ScienceDirect's AI-generated Topic Pages">treatment</a> is essential. Recently, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/reactive-oxygen-species" title="Learn more about reactive oxygen species from ScienceDirect's AI-generated Topic Pages">reactive oxygen species</a> (ROS)/JNK <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/signal-transduction" title="Learn more about signaling pathway from ScienceDirect's AI-generated Topic Pages">signaling pathway</a> has been proposed as the potential target for the <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/anticarcinogen" title="Learn more about anticancer drug from ScienceDirect's AI-generated Topic Pages">anticancer drug</a> discovery. The present study investigated the anticancer effects of the bioactive <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/xanthone-derivative" title="Learn more about xanthone from ScienceDirect's AI-generated Topic Pages">xanthone</a> garcinone E (GAR E) in mangosteen and explored its underlying mechanism of action. HT-29 and Caco-2 <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cancer-cell" title="Learn more about cancer cells from ScienceDirect's AI-generated Topic Pages">cancer cells</a> were used as in vitro models to study the anticancer effect of GAR E. The findings demonstrated that GAR E inhibited colony formation and wound healing, whereas triggered the production of ROS, which induced mitochondrial dysfunction and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/programmed-cell-death" title="Learn more about apoptosis from ScienceDirect's AI-generated Topic Pages">apoptosis</a>, causing <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cell-cycle-arrest" title="Learn more about cell cycle arrest from ScienceDirect's AI-generated Topic Pages">cell cycle arrest</a> at the Sub <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/g1-phase" title="Learn more about G1 phase from ScienceDirect's AI-generated Topic Pages">G1 phase</a>. Additionally, GAR E treatment elevated the ratio of Bax/Bcl-2 and activated PARP, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/caspase-3" title="Learn more about caspases 3 from ScienceDirect's AI-generated Topic Pages">caspases 3</a> and 9, and JNK1/2. These GAR E-induced cytotoxic activities and expression of signaling proteins were reversed by the antioxidant N-acetyl-L-cysteine and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/phosphotransferase-inhibitor" title="Learn more about JNK inhibitor from ScienceDirect's AI-generated Topic Pages">JNK inhibitor</a> <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/anthra1-9-cdpyrazol-6-2h-one" title="Learn more about SP600125 from ScienceDirect's AI-generated Topic Pages">SP600125</a>, indicating the involvement of ROS/JNK signaling pathways. <em>In vivo</em> experiments using an HT-29 <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/xenograft" title="Learn more about xenograft from ScienceDirect's AI-generated Topic Pages">xenograft</a> <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/nude-mouse" title="Learn more about nude mouse from ScienceDirect's AI-generated Topic Pages">nude mouse</a> model also demonstrated the antitumor effect of GAR E. In conclusion, our findings showed that GAR E might be potentially effective in treating colorectal cancer and provided insights into the development of xanthones as novel chemotherapeutic agents.</p>