Ceramides and Ceramide Synthases in Cancer: Focus on Apoptosis and Autophagy

Alizadeh, Javad; Rosa, Simone C. da Silva; Weng, Xiaohui; Jacobs, Joadi; Lorzadeh, Shahrokh; Ravandi, Amir; Vitorino, Rui; Pecic, Stevan; Shojaei, Shahla; Ghavami, Saeid

doi:10.20944/preprints202301.0264.v1

Cited by 7 publications

(5 citation statements)

References 222 publications

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“…Ceramides could regulate cellar apoptosis and autophagy in tumor and play the function suppressing tumor, so it possesses big potential to become tumor biomarker and drug target. [33] There are some strengths in this study. ( 1) it has rigorous design scheme.…”

Section: Discussionmentioning

confidence: 99%

Roles of plasma proteins in mediating the causal effect of the lipid species on gastric cancer and exploring potential drug targets for gastric cancer：insights from proteomic and two-step mendelian randomization and macromolecular docking

Dong,

Chen,

Zhao

et al. 2024

Preprint

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Background The change of plasma lipid species has close contacts with gastric cancer (GC). However, the specific mechanism still needs to explore further. Objectives We aim to utilize plasma proteins to decipher the association between lipid species and GC, and seek possible drug targets for GC. Methods A two-step mendelian randomization (MR) is conducted to identify the causal relationship among 179 lipid species, 4907 plasma proteins and GC. We employ the summary mendelian randomization (SMR) and colocalization to explore relationship between plasma proteins and GC. We use one protein data including 35559 individuals as discovery group, meanwhile the other one from 54219 subjects as validation group. MR is performed to identify the association between lipid species and GC or plasma proteins. Based on chosen proteins, we use macromolecular docking to find potential components as ligands. Results MR identifies the causality between 12 lipid species and GC, 3 proteins and GC, 2 lipid species and 2 proteins. After the test of propagation of error method, we conclude that CCDC80 protein mediates (30.8%; 95% confidents interval (Cl), 6.4%-64.0%) of the association between Diacylglycerol (16:1_18:1) and GC. For CCDC80, we choose 4 components including 2,3,7,8-Tetrachlorodibenzo-P-dioxin, Benzo[a]pyrene, Bisphenol A, Valproic Acid as potential drugs. Conclusion Our study suggests that CCDC80, a drug target, is a mediator between Diacylglycerol (16:1_18:1) and GC, which may guide a novel direction for GC treatment.

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Section: Discussionmentioning

confidence: 99%

Roles of plasma proteins in mediating the causal effect of the lipid species on gastric cancer and exploring potential drug targets for gastric cancer：insights from proteomic and two-step mendelian randomization and macromolecular docking

Dong,

Chen,

Zhao

et al. 2024

Preprint

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“…Autophagy relies on a coordinated collaboration among a group of proteins that collectively assemble autophagosomes and autolysosomes [263,264]. Additionally, selective cargo-recognizing proteins identify specific targets and guide them toward degradation [265,266].…”

Section: Nrf2 Modulates Autophagymentioning

confidence: 99%

NRF1 or NRF2: Emerging Role of Redox Homeostasis on PERK/NRF/Autophagy Mediated Antioxidant in Tumor and Patient Dependent Chemo Sensitivity

Dastghaib,

Shafiee,

Ramezani

et al. 2024

Preprint

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Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

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“…Autophagy is a natural "in-house" cleaning process that allows a stressed cell to breakdown cellular components and recycle/reuse some parts for efficient cellular processes (1,2). Many cells require autophagy to recycle damaged or stressed intracellular components for the purpose of maintaining homeostasis and cell health through both selective or non-selective degradative mechanisms (3,4).…”

Section: Introductionmentioning

confidence: 99%

Assessment of autophagy inLeishmaniaparasites

Onwah,

Uzonna,

Ghavami

2024

Preprint

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Leishmaniasis is a neglected tropical disease caused by numerous species ofLeishmaniaparasites, includingLeishmania major.The parasite is transmitted by several species of sandfly vectors and infects myeloid cells leading to a myriad of inflammatory responses, immune dysregulations, and disease manifestations. Every cell undergoes autophagy, a self-regulated degradative process that permits the cells to recycle damaged or worn-out organelles in order to maintain cellular health and homeostasis. Studies have shown thatLeishmaniamodulates their host cell autophagic machinery and there are indications that the parasite-specific autophagic processes may be valuable for parasite virulence and survival. However, the role of autophagy inLeishmaniais inconclusive because of the limited tools available to study theLeishmania-specific autophagic machinery. Here, we describe methods to study and definitively confirm autophagy inLeishmania major. Transmission electron microscopy (TEM) allowed us to visualizeLeishmaniaautophagosomes, especially those containing damaged mitochondrial content, as well as dividing mitochondria with ongoing fusion/fission processes. Flow cytometry enabled us to identify the amount of acridine orange dye accumulating in the acidic vacuolar compartments inLeishmania majorby detecting fluorescence in the red laser when autophagic inhibitors or enhancers were included. These methods will advance studies that aim to understand autophagic regulation inLeishmaniaparasites that could provide insights into developing improved therapeutic targets against leishmaniasis.

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Ceramides and Ceramide Synthases in Cancer: Focus on Apoptosis and Autophagy

Cited by 7 publications

References 222 publications

Roles of plasma proteins in mediating the causal effect of the lipid species on gastric cancer and exploring potential drug targets for gastric cancer：insights from proteomic and two-step mendelian randomization and macromolecular docking

Roles of plasma proteins in mediating the causal effect of the lipid species on gastric cancer and exploring potential drug targets for gastric cancer：insights from proteomic and two-step mendelian randomization and macromolecular docking

NRF1 or NRF2: Emerging Role of Redox Homeostasis on PERK/NRF/Autophagy Mediated Antioxidant in Tumor and Patient Dependent Chemo Sensitivity

Assessment of autophagy inLeishmaniaparasites

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