Toxoflavin analog D43 exerts antiproliferative effects on breast cancer by inducing ROS-mediated apoptosis and DNA damage - Details

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Triple-negative　breast　cancer　(TNBC)　is　regarded　as　the　deadliest　subtype　of　breast　cancer　because　of　its　high　heterogeneity,　aggressiveness,　and　limited　treatment　options.　Toxoflavin　has　been　reported　to　possess　antitumor　activity.　In　this　study,　a　series　of　toxoflavin　analogs　were　synthesized,　among　which　D43　displayed　a　significant　dose-dependent　inhibitory　effect　on　the　proliferation　of　TNBC　cells　(MDA-MB-231　and　HCC1806).　Additionally,　D43　inhibited　DNA　synthesis　in　TNBC　cells,　leading　to　cell　cycle　arrest　at　the　G2/M　phase.　Furthermore,　D43　consistently　promoted　intracellular　ROS　generation,　induced　DNA　damage,　and　resulted　in　apoptosis　in　TNBC　cells.　These　effects　could　be　reversed　by　N-acetylcysteine.　Moreover,　D43　significantly　inhibited　the　growth　of　breast　cancer　patient-derived　organoids　and　xenografts　with　a　favorable　biosafety　profile.　In　conclusion,　D43　is　a　potent　anticancer　agent　that　elicits　significant　antiproliferation,　oxidative　stress,　apoptosis,　and　DNA　damage　effects　in　TNBC　cells,　and　D43　holds　promise　as　a　potential　candidate　for　the　treatment　of　TNBC.　©　The　Author(s)　2024.

Keyword：

DNA damage N-acetylcysteine (NAC) Patient-derived breast cancer organoids (PDO) ROS Toxoflavin

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[ 1 ] [Wu T.]School of Life Science, University of Science & amp
[ 2 ] Technology of China, Anhui, Hefei, 230027, China, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China
[ 3 ] Technology of China, Anhui, Hefei, 230027, China, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China
[ 4 ] [Liu W.]The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China
[ 5 ] [Chen H.]Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fujian, Fuzhou, 350116, China
[ 6 ] [Hou L.]Department of Breast Disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & amp
[ 7 ] Henan Cancer Hospital, Zhengzhou, 450008, China
[ 8 ] [Ren W.]School of Life Science, University of Science & amp
[ 9 ] Technology of China, Anhui, Hefei, 230027, China, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China
[ 10 ] Technology of China, Anhui, Hefei, 230027, China, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China
[ 11 ] [Zhang L.]Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China
[ 12 ] [Hu J.]The First Hospital of Hunan University of Chinese Medicine, Hunan, Changsha, 410007, China
[ 13 ] [Chen H.]Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fujian, Fuzhou, 350116, China
[ 14 ] [Chen C.]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China
[ 15 ] [Chen C.]The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China
[ 16 ] [Chen C.]Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China

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Source ：

Scientific Reports

ISSN： 2045-2322

Year： 2024

Issue： 1

Volume： 14

3 . 8 0 0

JCR@2023

CAS Journal Grade：3

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ESI Highly Cited Papers on the List： 0 Unfold All

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