bims-midomi Biomed News
on MDM2 and mitochondria
Issue of 2026–07–26
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Sanggenon C induces P53-mediated apoptotic cell death associated with modulation of the MDM2-P53 axis in non-small cell lung cancer cells.
  2. Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Salivary Gland and Its Diagnostic Challenges: A Case Report and Literature Review.
  1. Food Chem Toxicol. 2026 Jul 21. pii: S0278-6915(26)00364-9. [Epub ahead of print] 116290
    Sanggenon C induces P53-mediated apoptotic cell death associated with modulation of the MDM2-P53 axis in non-small cell lung cancer cells.
    Yan Chen, Nanlan Xie, Yuanyuan Chen, Ling Ren, Weimin Zhu, Yijiao Huang, Yongfeng Shan, Pei Xiang.
      Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality and is characterized by disruption of P53-dependent cell death pathways. The present study investigated the effects of sanggenon C (SC), a natural polyphenolic compound, on cell death regulation focusing on the murine double minute 2 (MDM2)-P53 axis. SC was evaluated in NSCLC cell lines with different TP53 statuses and in xenograft and lung colonization models. SC preferentially induced apoptotic cell death in TP53 wild-type cells compared with TP53-mutant or TP53-null cells, accompanied by reduced clonogenic survival, migration, and invasion in P53-proficient cells, as well as decreased tumor burden and lung colonization in vivo in a TP53-dependent manner. Mechanistically, SC enhanced P53 protein stability by reducing ubiquitination and prolonging its half-life without altering TP53 mRNA expression, as demonstrated by cycloheximide chase and ubiquitination assays. DARTS-LC-MS/MS identified 72 candidate SC-associated proteins, and subsequent biochemical validation, including microscale thermophoresis and co-immunoprecipitation, implicated MDM2 as an SC-associated binding partner, further supported by molecular docking and molecular dynamics analyses. Consistently, SC decreased MDM2 protein abundance, while MDM2 overexpression partially attenuated SC-induced P53 stabilization. These findings indicate that SC induces P53-mediated apoptotic cell death in association with modulation of the MDM2-P53 axis.
    Keywords:  MDM2–P53 axis; Sanggenon C; apoptotic cell death; non-small cell lung cancer; ubiquitination
    DOI:  https://doi.org/10.1016/j.fct.2026.116290
  2. Int J Surg Pathol. 2026 Jul 22. 10668969261458405
    Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Salivary Gland and Its Diagnostic Challenges: A Case Report and Literature Review.
    Breera Khan, Javaria Khan, Youssef Al Hmada, Syed Abbas.
      Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is a low-grade adipocytic neoplasm composed of mature adipocytes with at least focal nuclear atypia in adipocytes and stromal cells. The terms "atypical lipomatous tumor" and "well-differentiated liposarcoma" are site-dependent terms for the same morphological and genetic entity. Amplification of MDM2 and/or CDK4 is almost always present and is a defining molecular feature. It usually arises in deep soft tissue. Primary head-and-neck involvement is rare, and salivary gland tumors are exceptionally uncommon. Only a few salivary gland tumors have been reported and accurate diagnosis may be challenging because they can mimic benign lipomatous lesions. ALT lacks metastatic potential unless dedifferentiation occurs, but it carries a significant risk of local recurrence. Careful histology plus MDM2 gene testing improves diagnostic accuracy. We report a 59-year-old man presenting with a recurrent parotid mass 7 years after a lipoma excision at an outside facility. Imaging showed involvement of both superficial and deep lobes of the left parotid gland. The facial nerve was preserved during surgery, and the postoperative course was uneventful. Histologic examination of the reexcision specimen showed mature adipose tissue with adipocyte size variation and focal atypia within fibrous septa; fluorescence in situ hybridization confirmed MDM2 amplification, establishing ALT. This case report aims to highlight the diagnostic challenges of ALT in uncommon locations such as the parotid gland and to evaluate strategies for accurate recognition and effective management, with emphasis on avoiding misdiagnosis and ensuring complete surgical excision.
    Keywords:  MDM2 gene; atypical lipomatous tumor; case report; parotid gland; salivary gland tumors; well-differentiated liposarcoma
    DOI:  https://doi.org/10.1177/10668969261458405
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