bims-midomi Biomed News
on MDM2 and mitochondria
Issue of 2026–08–16
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Garcinoic acid promotes ferroptosis-associated growth inhibition in esophageal squamous cell carcinoma through an MDM2-associated mechanism.
  2. GSG2 promotes aerobic glycolysis and colorectal cancer progression via the MDM2-p53 axis.
  1. Transl Cancer Res. 2026 Jul 31. 15(7): 520
    Garcinoic acid promotes ferroptosis-associated growth inhibition in esophageal squamous cell carcinoma through an MDM2-associated mechanism.
    Li-Ying Sun, Peng Huang, Yan-Hua Su.
       Background: Garcinoic acid (GA), a plant metabolite, has been shown to exhibit anti-inflammatory and antioxidant activities; however, its mechanism of action against esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to investigate the effects of GA on ESCC and to elucidate its underlying molecular mechanisms.
    Methods: The anti-ESCC effects of GA were evaluated using cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, acridine orange/ethidium bromide (AO/EB) staining, and Transwell assays. Ferroptosis-associated changes were assessed using C11-BODIPY staining, reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and glutathione (GSH) assays, transmission electron microscopy, and Western blotting of ferroptosis-associated proteins. Network pharmacology and Mendelian randomization were employed to prioritize candidate mediators linking GA, ESCC, and ferroptosis. Molecular docking and molecular dynamics simulations were performed to predict potential GA-mouse double minute 2 (MDM2) interactions and assess complex stability. Rescue experiments were conducted to evaluate the functional relevance of MDM2.
    Results: GA inhibited ESCC cell proliferation, induced apoptosis, and reduced cell migration. GA increased levels of MDA and Fe2+, and induced GSH depletion. Pretreatment with Ferrostatin-1 attenuated GA-induced inhibition of cell viability. MDM2 was prioritized as a candidate mediator linking GA, ESCC, and ferroptosis. Molecular docking predicted a favorable binding affinity between GA and MDM2, with a binding energy of -9.1 kcal/mol. Molecular dynamics simulations suggested that the predicted GA-MDM2 complex remained stable under the simulation conditions. Rescue experiments demonstrated that MDM2 may mediate GA-associated ferroptosis and growth inhibition in ESCC cells.
    Conclusions: These findings suggest that GA induces ferroptosis-associated growth inhibition in ESCC cells, potentially through an MDM2-associated mechanism, and provide a rationale for further investigation of GA-related ferroptosis modulation in ESCC.
    Keywords:  Garcinoic acid (GA); esophageal squamous cell carcinoma (ESCC); ferroptosis; mouse double minute 2 (MDM2)
    DOI:  https://doi.org/10.21037/tcr-2025-1-2729
  2. Am J Cancer Res. 2026 ;16(7): 3066-3083
    GSG2 promotes aerobic glycolysis and colorectal cancer progression via the MDM2-p53 axis.
    Hua Pan, Jipeng Liu, Taifu Xiao, Jun Huang.
      Colorectal cancer (CRC) is the third most common type of cancer worldwide and ranks among the leading causes of cancer-related deaths. During tumor progression, post-translational modifications, mainly the ubiquitin-proteasome system, are critical mediators of cellular metabolic reprogramming, including the metabolic changes of tumor development. Although TP53 mutations occur in approximately half of all CRC cases and could define their genetic makeup, precise therapeutic vulnerabilities remain largely unknown for the subgroup with wild-type p53. This study investigated the significant expression of Germ Cell-Specific Gene 2 (GSG2) in CRC. We demonstrated GSG2 is strongly increased in malignant colorectal tissues compared with adjacent benign tissues, and this high expression strongly predicts poor patient survival. Additionally, the results indicate that removing GSG2 effectively suppresses tumor growth in both in vitro systems and in vivo xenograft models. Mechanistically, GSG2 directly binds to the E3 ligase MDM2, and promoted MDM2-mediated ubiquitination and degradation of p53 in p53 wild-type CRC cells. Consequently, GSG2 enhances the cellular metabolic program, reprogramming glucose use toward aerobic glycolysis to meet the energy needs of uncontrolled growth. Thus, our findings reveal a novel way that p53 is silenced in cancers with wild-type TP53. GSG2 demonstrate control of the MDM2-p53 axis to promote the Warburg effect and drive CRC progression via p53 suppression.
    Keywords:  GSG2; MDM2; P53; aerobic glycolysis; colorectal cancer
    DOI:  https://doi.org/10.62347/WEGW4871
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