13027-33-3Relevant articles and documents
Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner
Mgrditchian, Takouhie,Arakelian, Tsolere,Paggetti, Jér?me,Noman, Muhammad Zaeem,Viry, Elodie,Moussay, Etienne,Van Moer, Kris,Kreis, Stephanie,Guerin, Coralie,Buart, Stephanie,Robert, Caroline,Borg, Christophe,Vielh, Philippe,Chouaib, Salem,Berchem, Guy,Janji, Bassam
, p. E9271 - E9279 (2017/11/07)
While blocking tumor growth by targeting autophagy is well established, its role on the infiltration of natural killer (NK) cells into tumors remains unknown. Here, we investigate the impact of targeting autophagy gene Beclin1 (BECN1) on the infiltration of NK cells into melanomas. We show that, in addition to inhibiting tumor growth, targeting BECN1 increased the infiltration of functional NK cells into melanoma tumors. We provide evidence that driving NK cells to the tumor bed relied on the ability of autophagy-defective tumors to transcriptionally overexpress the chemokine gene CCL5. Such infiltration and tumor regression were abrogated by silencing CCL5 in BECN1-defective tumors. Mechanistically, we show that the up-regulated expression of CCL5 occurred through the activation of its transcription factor c-Jun by a mechanism involving the impairment of phosphatase PP2A catalytic activity and the subsequent activation of JNK. Similar to BECN1, targeting other autophagy genes, such as ATG5, p62/SQSTM1, or inhibiting autophagy pharma-cologically by chloroquine, also induced the expression of CCL5 in melanoma cells. Clinically, a positive correlation between CCL5 and NK cell marker NKp46 expression was found in melanoma patients, and a high expression level of CCL5 was correlated with a significant improvement of melanoma patients’ survival. We believe that this study highlights the impact of targeting autophagy on the tumor infiltration by NK cells and its benefit as a novel therapeutic approach to improve NK-based immunotherapy.
Synthesis and plant growth promoting activity of polyhydroxylated ketones bearing the 5α-hydroxy-6-oxo moiety and cholestane side chain
Rosado-Abón, Anielka,De Dios-Bravo, Guadalupe,Rodríguez-Sotres, Rogelio,Iglesias-Arteaga, Martín A.
experimental part, p. 461 - 466 (2012/05/19)
Three polyhydroxylated ketones bearing the 5α-hydroxy-6-oxo moiety were obtained from cholesterol. Two of them show plant growth promoting activity in the bean's second internode bioassay. The obtained results indicate that the presence of the 5α-hydroxy-
Kinetic model for studying the effect of quercetin on cholesterol oxidation during heating
Chien, John-Tung,Hsu, Da-Jung,Chen, Bing-Huei
, p. 1486 - 1492 (2007/10/03)
Inhibition of the heat-induced cholesterol oxidation at 150°C by incorporation of quercetin was kinetically studied. Results showed that without quercetin, the cholesterol oxidation products (COPs) concentration increased with increasing heating time. A low amount (0.002%, w/w) of quercetin was effective in inhibiting the formation of COPs during the initial heating period (≤30 min) at 150°C. However, after prolonged heating (30-120 min), a low antioxidant activity was observed because of the degradation of quercetin. When using nonlinear regression models for kinetic study of cholesterol oxidation in the absence of quercetin, the epoxidation showed the highest rate constant (h-1 = 683.1), followed by free radical chain reaction (h -1 = 453.5), reduction (h-1 = 290.3), dehydration (h -1 = 155.5), triol dehydrogenation (h-1 = 5.35), dehydrogenation (h-1 = 0.68), thermal degradation (h-1 = 0.66), and triol formation (h-1 = 0.38). However, in the presence of quercetin, the reaction rate constants (h-1) for epoxidation (551.4), free radical chain reaction (111.7), and thermal degradation (0.28) were reduced greatly. The kinetic model developed in this study can be used to predict the inhibition of COPs by quercetin during the heating of cholesterol.
