ArticleCancer immunology, immunotherapy : CII2020
PKCζ mediated anti-proliferative effect of C2 ceramide on neutralization of the tumor microenvironment and melanoma regression.
Article in Cancer immunology, immunotherapy : CII, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Identification and validation of a sphingolipid metabolism-related prognostic signature for predicting prognosis and immune microenvironment-related characteristics in ovarian cancer.Translational cancer research · 2026Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024Review
- Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment.Molecules (Basel, Switzerland) · 2024Review
- Article
- G3BP1 regulates breast cancer cell proliferation and metastasis by modulating PKCζ.Frontiers in genetics · 2022Article
- The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Frontiers in oncology · 2022Review
- Cytochrome P450 1A1 is essential for the microbial metabolite, Urolithin A-mediated protection against colitis.Frontiers in immunology · 2022Article
- The Role of Sphingolipids in Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Cancer stem cells and ceramide signaling: the cutting edges of immunotherapy.Molecular biology reports · 2020Review
- Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Immunotherapy, which has advantages over chemotherapy due to lesser toxicity and higher specificity, is on the rise to treat cancer. Recently, pro-apoptotic glycolipid, ceramide has emerged as a key regulator in cancer immunotherapy. The present study elucidated the potential anti-melanoma efficacy of cell-permeable, exogenous C2 ceramide on cell death and amelioration of tumor microenvironment (TME). We, for the first time, demonstrated that C2 ceramide triggered apoptosis of melanoma cells by augmenting PKCζ along with pro-inflammatory cytokines and signaling factors. C2 ceramide showed a PKCζ-mediated tumor-suppressive role in melanoma without exhibiting hepatotoxicity and nephrotoxicity. Moreover, PKCζ was revealed as one of the key regulators of Akt and ceramide during C2 ceramide-mediated apoptosis. C2 ceramide was effective in repolarization of M2 macrophage phenotype and reduction of angiogenic factors such as VEGF, VEGFR1, VEGFR2, HIF1α. Interestingly, PKCζ knockdown attenuated C2 ceramide-mediated inhibition of melanoma progression. Restoration of the Th1 type TME by C2 ceramide enhanced cytotoxic T cell-mediated killing of melanoma cells. Altogether, the study unraveled that C2 ceramide-induced PKCζ was associated with favorable immune cell functioning in TME leading to melanoma regression. Thus, our findings explored a novel mechanistic insight into C2 ceramide as a promising immunotherapeutic agent in melanoma treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.