Data from Inhibition of Lysosomal Function Mitigates Protective Mitophagy and Augments Ceramide Nanoliposome–Induced Cell Death in Head and Neck Squamous Cell Carcinoma

التفاصيل البيبلوغرافية
العنوان: Data from Inhibition of Lysosomal Function Mitigates Protective Mitophagy and Augments Ceramide Nanoliposome–Induced Cell Death in Head and Neck Squamous Cell Carcinoma
المؤلفون: Mark Kester, Todd E. Fox, Mark J. Jameson, Pedro Costa-Pinheiro, Michael H. Raymond, Alexandra Hickman, Tara Caste, Tristen Slamowitz, Patrick J. Beck, Emily Venner, Timothy L. Boyer, Jeremy J.P. Shaw
بيانات النشر: American Association for Cancer Research (AACR), 2023.
سنة النشر: 2023
الوصف: Therapies for head and neck squamous cell carcinoma (HNSCC) are, at best, moderately effective, underscoring the need for new therapeutic strategies. Ceramide treatment leads to cell death as a consequence of mitochondrial damage by generating oxidative stress and causing mitochondrial permeability. However, HNSCC cells are able to resist cell death through mitochondria repair via mitophagy. Through the use of the C6-ceramide nanoliposome (CNL) to deliver therapeutic levels of bioactive ceramide, we demonstrate that the effects of CNL are mitigated in drug-resistant HNSCC via an autophagic/mitophagic response. We also demonstrate that inhibitors of lysosomal function, including chloroquine (CQ), significantly augment CNL-induced death in HNSCC cell lines. Mechanistically, the combination of CQ and CNL results in dysfunctional lysosomal processing of damaged mitochondria. We further demonstrate that exogenous addition of methyl pyruvate rescues cells from CNL + CQ–dependent cell death by restoring mitochondrial functionality via the reduction of CNL- and CQ-induced generation of reactive oxygen species and mitochondria permeability. Taken together, inhibition of late-stage protective autophagy/mitophagy augments the efficacy of CNL through preventing mitochondrial repair. Moreover, the combination of inhibitors of lysosomal function with CNL may provide an efficacious treatment modality for HNSCC.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88e9505519539f89dd00230139069196
https://doi.org/10.1158/1535-7163.c.6542178
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....88e9505519539f89dd00230139069196
قاعدة البيانات: OpenAIRE