ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
This article is part of the Research TopicCell Death: A New Frontier in Cancer ResearchView all 6 articles
Garciniagifolone A, Derived from Garcinia Multiflora Fruits, Inhibits Triple-Negative Breast Cancer Cells and Organoids Growth by Targeting CA9
Provisionally accepted
Fulin Zhou1
Siyu Yang2Qiang Lin2Ruling Zhang3Yingshi Su4Yibo Hou5Jin Wang4
Jiaye Mo6
Yubo Zhang2
Xiaoyong Dai2*
Shu Liu7- 1Guiyang Maternity and Child Health Hospital, Guiyang, China
- 2Jinan University, Guangzhou, China
- 3Guiyang Healthcare Vocational University, Guiyang, China
- 4Synorg Biotechnology (Shenzhen) Co. Ltd., Shenzhen, China
- 5Tsinghua Shenzhen International Graduate School, Shenzhen, China
- 6GuangXi University of Chinese Medicine, Nanning, China
- 7Guizhou Medical University, Guiyang, China
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The Garcinia multiflora. is not only a delicious fruit that can be consumed directly, but also contains abundant medicinal components in anti-inflammatory and anti-tumor treatments. The objective of this study was to clarify the anti-tumor properties and the underlying mechanism of garciniagifolone A (GA), a polycyclic polyprenylated acylphloroglucinol derived from the edible fruits of Garcinia multiflora, in triple-negative breast cancer (TNBC). Herein, we demonstrated that GA exhibited inhibitory effects on TNBC organoids growth, and suppressed the proliferation, colony formation, migration, and invasion of TNBC cells in vitro. Moreover, GA demonstrated a significant suppression of TNBC growth in vivo without apparent toxicity, and it augmented the anti-tumor efficacy of PTX in both TNBC organoids and xenograft models. GA specifically bound with carbonic anhydrase IX (CA9), a target overexpressed in TNBC and linked to poor prognosis, as confirmed by molecular docking, surface plasmon resonance, and cellular thermal shift assays. Mechanistically, GA binding to CA9 suppresses the PI3K/AKT/mTOR pathway, inducing early-stage autophagy initiation evidenced by increased LC3B-II/I ratio and autophagosomes. However, GA concurrently blocked autophagic flux by inhibiting autophagosome-lysosome fusion, leading to p62 accumulation and reactive oxygen species (ROS) overproduction. Elevated ROS by GA activated the JNK pathway and triggered NLRP3 inflammasome assembly, resulting in caspase-1-mediated cleavage of gasdermin D (GSDMD) and subsequent pyroptosis, alongside caspase-3-dependent apoptosis. Collectively, GA exerted its potent anti-TNBC activity by targeting CA9 to dysregulate autophagy and induce ROS-mediated pyroptosis/apoptosis, presenting a promising low-toxicity therapeutic strategy.
Keywords: Autophagy, Carbonic Anhydrase IX, Garciniagifolone A, PI3K/Akt/mTOR pathway, pyroptosis, TNBC
Received: 14 Dec 2025; Accepted: 06 Feb 2026.
Copyright: © 2026 Zhou, Yang, Lin, Zhang, Su, Hou, Wang, Mo, Zhang, Dai and Liu. 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: Xiaoyong Dai
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