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Pyrrolizidine Alkaloids
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
As PA clivorine is shown to induce apoptotic cell death and oxidative stress injury in human normal liver L-02 cells, a plant-derived flavonoid called quercetin is being trialed for preventing clivorine-induced apoptotic cell death. Through upregulation of oxidative or metabolic stress-related genes (e.g., Fmo5, Polr2k, Sod2, Ephx2, Sod1, Hmox2, Hmox1, Cyp2b10, Cyp1b1, Cyp2a5, Cyp3a11, and Cyp7a1) and heat shock–related genes (e.g., Hspa5, Hspa1 l, Hspa1b, Dnaja1, and Hspe1), quercetin works to increase the level of liver GSH (which is an important endogenous antioxidant), and to ameliorate clivorine-induced oxidative stress [34].
BAG1, MGMT, FOXO1, and DNAJA1 as potential drug targets for radiosensitizing cancer cell lines
Published in International Journal of Radiation Biology, 2023
Bayanika Manunu, Antonio M. Serafin, John M. Akudugu
Inhibition of the radiation-induced overexpression of DNAJA1 in A549 (∼65-fold upregulation) by 116-9e led to a reduction in cell survival under the stress generated by ionizing radiation. Overexpression of DNAJA1 has been reported to reduce pancreatic cancer cell survival under stress (Stark et al. 2014). The marginal DNAJA1 upregulation in the G28 cell line is, therefore, consistent with apparent increase in radioresistance. DnaJ (Hsp40) are proteins that act as co-chaperones to the molecular chaperone DnaK (Hsp70). The major stress protein, Hsp70, is overexpressed in a variety of tumors, probably because cancer cells demonstrate rapid and strong metabolism and enhanced protein synthesis that require a higher level of cellular chaperones to regulate the correct folding of proteins and their transport to target cellular organelles (Stark et al. 2014).
Single-cell analysis reveals immune modulation and metabolic switch in tumor-draining lymph nodes
Published in OncoImmunology, 2020
Yen-Liang Li, Chung-Hsing Chen, Jing-Yi Chen, You-Syuan Lai, Shao-Chun Wang, Shih-Sheng Jiang, Wen-Chun Hung
In addition to the above pathway-level analysis, we also performed analysis at single gene level to identify differentially expressed genes (DEGs, Supplementary Table S1) whose expression levels were significantly altered between cells from TDLNs and those from naïve LNs. Among the top upregulated DEGs identified in the CD4 + T cells were genes encoding heat shock proteins, including Dnaja1, Dapl, Hspa1a, Dapl and Hsp90ab1, whose expression patterns were represented by violin plot in Figure 2e. Interestingly, these chaperone proteins are known to be involved in immune modulation. For examples, Hspa1a encodes a heat shock protein which is a member of Hsp70 family; HSP70 in combination with IL-2 may enhance secretion of the immunosuppressive cytokines IL-10 and TGF-β from Tregs cells, while attenuating the activity of CD4+ CD25− naive T cells.37Dapl1 expressed on Nrp-1-negative cells may represent a subgroup of peripherally induced Tregs cells with immunosuppressive activity.38 Moreover, Hsp90ab1, a member of the Hsp90 family, has been shown to play a role in the regulation of autoimmunity and transplant rejection.39
The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery
Published in Expert Review of Molecular Diagnostics, 2023
Nicola Antonio di Meo, Francesco Lasorsa, Monica Rutigliano, Martina Milella, Matteo Ferro, Michele Battaglia, Pasquale Ditonno, Giuseppe Lucarelli
Statin usage has also been linked to better OS and Disease-Specific Survival (DSS) in patients who underwent surgery for localized RCC [137,138]. In a case study of 850 patients who underwent surgery for localized RCC, statin users reported prolonged Recurrence-Free Survival (RFS, +46%) and OS (+55%) [139]. Statins may slow the progression of kidney and PCa through a variety of cholesterol- and non-cholesterol-mediated mechanisms, which could explain the reported increase in survival [128]. According to Thompson et al. [140], statins have a significant cytotoxic effect on von Hippel-Lindau (VHL) gene-deficient RCC cell lines. Mevalonate-5-phosphate is a step in the mevalonate pathway. It stabilizes conformational or misfolded mutant p53, which increases the production of enzymes in the mevalonate pathway. Statins decrease the formation of FPP and GGPP, mutated p53, and the mevalonate pathway, which inhibits the prenylation of Ras and Rho [141–143]. Some statins target additional cancer-related molecules in addition to inhibiting the binding site in HMGCR and exhibit potential as anti-cancer drugs. Statins cause the breakdown of mutant p53 by preventing it from interacting with DNAJA1. Statins’ effects are lessened by DNAJA1 chaperone overexpression and ubiquitin ligase CHIP downregulation. The effect on wild-type p53 or DNA contact mutp53 with native conformation is modest [142]. Some statins are also substrates for the organic anionic transporter SLCO2B1. This transporter blocks the movement of dehydroepiandrosterone sulfate, which is a precursor to more powerful androgens [143]. The role of statins was examined in various PCa stages, with notable results.