- |||||||||| hydroxychloroquine / Generic mfg., docetaxel / Generic mfg.
Golgi disorganization and ER stress: the mechanism underlying alcohol-mediated prostate cancer progression (Section 5; Poster Board #20) - Mar 14, 2023 - Abstract #AACR2023AACR_4334;
We have found a positive correlation between the number of Golgi fragments and the intensity of Integrin ?v on the PM in both docetaxel-resistant PC-3 and DU145 cells after EtOH treatment...We found that autophagy inhibitor, Hydroxychloroquine (HCQ), restores compact Golgi in both PC-3 and DU145 cells, as well as in mice orthotopic PC-3-derived tumors...We expect that our established protocol to restore Golgi morphology and inhibit ER stress by HCQ treatment and ATF6 depletion, respectively, will attenuate the impact of EtOH on PCa cells. Overall, these data shed light on alcohol-promoting effects on prostate tumor growth and metastasis and provide a potentially effective therapeutic strategy.
- |||||||||| CEP-11981 / Teva
Novel autophagy inhibitor ESK981 potentiates MEK inhibition cytotoxicity in pancreatic cancer (Section 17; Poster Board #24) - Mar 14, 2023 - Abstract #AACR2023AACR_3879;
Finally, using Cell-Titer Glo, we determined that ESK981 and Trametinib had a strong synergistic effect on suppressing cell proliferation (BLISS Score >20) on mouse KPC line 7940B. Taken together, ESK981 is a promising autophagy inhibitor that shows strong anti-proliferative effects on both human and mouse PDAC cell lines as a single agent as well as in combination with Trametinib.
- |||||||||| Mekinist (trametinib) / Novartis
Autophagy and MEK inhibition promotes ferroptosis in liver kinase B1 (Lkb1)-deficient Kras-driven lung tumors (Section 10; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_2796;
Taken together, our observations indicate that autophagy upregulation in KL tumors causes resistance to Trametinib treatment by maintaining energy homeostasis for cell survival and inhibits ferroptosis. Therefore, a combination of autophagy and MEK inhibition could be a novel therapeutic strategy to specifically treat LKB1-deficient KRAS-driven NSCLC.
- |||||||||| GSK2816126 / GSK
Simultaneous inhibition of EZH2 and activation of dopamine D1 in an isotropic triple-negative breast cancer microgel model (Section 12; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_2701;
Tumor spheroids formed after 2 days were subjected to single and combination therapies of GSK126, an EZH2 inhibitor, and A77636, a dopamine agonist over the span of 4 days...Furthermore, knockout of EZH2 in the TNBC cells resulted in inability for tumor spheroid formation and a sensitivity to A77636. Our findings imply that EZH2 is critical for spheroid formation and growth in TNBC and suggest that targeting the EZH2 alongside D1R presents a novel strategy for enhancing EZH2 inhibition
- |||||||||| Characterization of a novel series of highly selective PARP7 inhibitors (Section 17; Poster Board #17) - Mar 14, 2023 - Abstract #AACR2023AACR_2547;
and CXCL10. In summary, we describe the characterization of a lead series of highly potent and selective PARP7 inhibitors which demonstrate excellent in vitro ADMET and in vivo PK properties leading to best-in-class anti-tumor efficacy in a KRAS-driven lung cancer xenograft model.
- |||||||||| JQ-1 / Roche
Novel autophagy inhibitory strategies to overcome chemotherapy resistance in multiple myeloma (Section 16; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_2463;
Classical chemotherapeutics including bortezomib, melphalan, lenalidomide and thalidomide have greatly enhanced survival times...The BRD4 inhibitor, JQ1, effectively impairs the tumorigenic potential of MM but resistance has also been noted...We also show by EMMA ex vivo platform that MA9060 is highly effective for the treatment of CD138+ MM cells isolated from patients with refractory disease.ULK3 represents a novel target for treatment of MM refractory disease. Our dual inhibitors can increase overall survival in vivo and ex vivo, therefore we expect to quickly translate our novel molecules to the clinic.
- |||||||||| Journal: Circ-calm4 regulates hypoxia-induced pulmonary artery smooth muscle autophagy by binding Purb. (Pubmed Central) - Mar 13, 2023
Interestingly, we found that Beclin1 transcription initiated by Purb was accompanied by a modification of Beclin1 super-enhancer to improve transcription activity and efficiency. Overall, our results confirm that the circ-calm4/Purb/Beclin1 signal axis is involved in the occurrence of hypoxia-induced PASMCs autophagy, and the novel regulatory mechanisms and signals transduction pathways in PASMC autophagy induced by hypoxia.
- |||||||||| Journal: A plant virus hijacks phosphatidylinositol-3,5-bisphosphate to escape autophagic degradation in its insect vector. (Pubmed Central) - Mar 13, 2023
Furthermore, we show that PtdIns(3,5)P inhibits the autophagy pathway by preventing the fusion of autophagosomes and lysosomes through activation of Trpml (transient receptor potential cation channel, mucolipin), an effector of PtdIns(3,5)P. These findings uncover a strategy whereby a plant virus hijacks PtdIns(3,5)P via its viral capsid protein to evade autophagic degradation and promote its survival in insects.
- |||||||||| sirolimus / Generic mfg.
Journal: Quantitative and temporal measurement of dynamic autophagy rates. (Pubmed Central) - Mar 13, 2023
We use this approach to measure temporal responses to rapamycin and wortmannin treatments, two commonly used autophagy modulators...Glutamine starvation led to a decrease in the rates on a longer timescale. In summary, this new approach enables the quantification of autophagy flux with high sensitivity and temporal resolution and facilitates a comprehensive understanding of this process.
- |||||||||| deferiprone / Generic mfg.
Journal: Palmitic acid-induced ferroptosis via CD36 activates ER stress to break calcium-iron balance in colon cancer cells. (Pubmed Central) - Mar 12, 2023
Subsequently, we verified that PA induces ferroptotic cell death through excess iron as cell death was inhibited by iron chelator deferiprone (DFP), while it was exacerbated by a supplement of ferric ammonium citrate (FAC)...Furthermore, we observed that cells with high expression of CD36 were more vulnerable to PA-induced ferroptosis. Altogether, our findings reveal that PA engages in anticancer properties by activating ER stress/ER calcium release/transferrin-dependent ferroptosis, and PA might serve as a compound to activate ferroptosis in colon cancer cells with high CD36 expression.
- |||||||||| Review, Journal: Research Progress on the Anticancer Molecular Mechanism of Targets Regulating Cell Autophagy. (Pubmed Central) - Mar 9, 2023
Therefore, this review article describes the mechanism of autophagy, the role of autophagy in normal cells and tumor cells, and the research progress on the anticancer molecular mechanism of targets regulating cell autophagy. The aim is to provide a theoretical basis for developing autophagy inhibitors or activators to improve anticancer efficacy.
- |||||||||| temozolomide / Generic mfg.
Journal: Leucine-rich repeats containing 4 protein (LRRC4) in memory, psychoneurosis, and glioblastoma. (Pubmed Central) - Mar 9, 2023
LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.
- |||||||||| Journal: Sinomenine promotes flap survival by upregulating eNOS and eNOS-mediated autophagy via PI3K/AKT pathway. (Pubmed Central) - Mar 9, 2023
Having a therapeutic benefit of SIN, Autophagy inhibitor 3-MA shows its critical role by reversing the beneficial effects of SIN, and the nitric oxide synthase inhibitor l-NAME both stimulated HUVECs that explore the relationship between autophagy flux and nitric oxide synthase. Furthermore, the mechanism in our study reveals the changes in the signal pathway of PI3K/AKT, the protective effect of SIN during antioxidant activity, the activation of eNOS through PI3K/AKT signaling pathway affects autophagy through the eNOS system, and promote the random flap survival.
- |||||||||| vesatolimod (GS-9620) / Gilead
Preclinical, Journal, IO biomarker: Neuroprotective effect of Vesatolimod in an experimental autoimmune encephalomyelitis mice model. (Pubmed Central) - Mar 9, 2023
Furthermore, the mechanism in our study reveals the changes in the signal pathway of PI3K/AKT, the protective effect of SIN during antioxidant activity, the activation of eNOS through PI3K/AKT signaling pathway affects autophagy through the eNOS system, and promote the random flap survival. Our results indicate that Vesatolimod exhibits protective effects on EAE mice and is promising for treatment of MS.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Kirenol inhibits inflammation challenged by lipopolysaccharide through the AMPK-mTOR-ULK1 autophagy pathway. (Pubmed Central) - Mar 9, 2023
Moreover, inhibition of autophagy using AMPK inhibitor or 3-MA or chloroquine (CQ) reversed the anti-inflammatory and autophagy-enhancement effects of kirenol exposure in vitro, indicating that kirenol could enhance autophagy by activating the AMPK-mTOR-ULK1 pathway...Further in vivo ALI mouse model studies demonstrated the protective role of kirenol against lung inflammation, such as improved histopathology, decreased lung edema, and leukocyte infiltration were abolished by 3-MA. These findings implicate that kirenol can inhibit LPS-induced inflammation via the AMPK-mTOR-ULK1 autophagy pathway.
- |||||||||| bleomycin / Generic mfg.
Journal: IL-27 induces autophagy through regulation of the DNMT1/lncRNA MEG3/ERK/p38 axis to reduce pulmonary fibrosis. (Pubmed Central) - Mar 9, 2023
In summary, pNaktide attenuates neuroinflammation, reduces the level of oxidative stress, has neuroprotective effects, and may be used for the treatment of neuroinflammation-related diseases. In conclusion, our study shows that IL-27 upregulates MEG3 expression through inhibition of DNMT1-mediated lncRNA MEG3 promoter methylation, which in turn inhibits ERK/p38 signaling pathway-induced autophagy and attenuates BLM-induced PF, providing a contribution to the elucidation of the potential mechanisms by which IL-27 attenuates PF.
- |||||||||| Review, Journal: The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates. (Pubmed Central) - Mar 8, 2023
The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.
- |||||||||| chloroquine phosphate / Generic mfg., cisplatin / Generic mfg.
Journal: Research on the role of cellular autophagy in the sensitivity of human tongue cancer cells to radiotherapy and chemotherapy. (Pubmed Central) - Mar 7, 2023
As such, PRL2 is a potential therapeutic target for inflammatory bone disease and inhibition of HSC70 mediated autophagic degradation of PRL2 may offer new therapeutic tools for the treatment of inflammatory bone disease. Tca8113 cells upregulated autophagy under the effect of either radiation or cisplatin, and the sensitivity of Tca8113 cells to cisplatin and radiation could be improved by inhibiting autophagy using multiple pathways.
- |||||||||| chloroquine phosphate / Generic mfg., hydroxychloroquine / Generic mfg., itraconazole / Generic mfg.
Journal: Repurposing Itraconazole and Hydroxychloroquine to Target Lysosomal Homeostasis in Epithelial Ovarian Cancer. (Pubmed Central) - Mar 7, 2023
P1/2
The drug combination had no clinical antitumor activity in dose escalation. The combination of the antifungal drug itraconazole with antimalarial drug hydroxychloroquine leads to a cytotoxic lysosomal dysfunction, supporting the rational for further research on lysosomal targeting in ovarian cancer.
- |||||||||| sirolimus / Generic mfg.
Journal: Autotaxin (ATX) inhibits autophagy leading to exaggerated disruption of intestinal epithelial barrier in colitis. (Pubmed Central) - Mar 6, 2023
This pro-colitic effect was attenuated in mice treated with rapamycin, resulting in increased autophagy activity and mild colitis...In sum, our results show that ATX can inhibit autophagy through the mTOR pathway, resulting in exaggerated damage to the intestinal epithelial barrier during colitis. These findings suggest that ATX may be a key pro-colitic factor, and represent a potential therapeutic target for treating IBD in the future.
- |||||||||| Journal: Ferritin-dependent cellular autophagy pathway promotes ferroptosis in beef during cold storage. (Pubmed Central) - Mar 6, 2023
These findings suggest that ATX may be a key pro-colitic factor, and represent a potential therapeutic target for treating IBD in the future. Furthermore, treatment of myoblasts with GSK 2656157 (autophagy inhibitor) showed that ferritin degradation was lower in the GSK 2656157-treated myoblasts than in the control, while GSH content and GPX4 activity were higher than the control (P
- |||||||||| Depletion of ARMS in melanoma cells induces autophagy-mediated cell death under oxidative stress () - Mar 4, 2023 - Abstract #ISID2023ISID_1423;
In addition, we found that knockdown of ARMS inhibited H 2 O 2 -induced activation of nuclear factor-kappa B signaling pathway and repressed the expression of antioxidant proteins catalase and SOD1 in melanoma cells. Our results suggest silencing ARMS as an alternative therapeutic strategy in treating apoptosis-resistant melanomas by activating ROS-induced autophagy-mediated cell death.
- |||||||||| Dysregulation of N6-methyladenine DNA methylation as a new epigenetic mechanism in skin tumorigenesis (ePoster Stage 2; Poster Hall space (NS Building)) - Mar 4, 2023 - Abstract #ISID2023ISID_451;
Taken together, our findings provide a critical new layer of epigenetic regulation of gene expression in skin tumorigenesis. Our findings may open up new opportunities for developing new preventive and therapeutic strategies to reduce skin cancer burden by targeting 6mA DNA methylation and ALKBH4.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses. (Pubmed Central) - Mar 2, 2023
In conclusion, we showed the metabolites from the probiotic, L. plantarum, work synergistically with chloroquine in killing Caco-2 cells and downregulating the expression of autophagy-related proteins, suggesting the involvement of autophagy, rather than apoptosis, in their cytotoxic effect. Hence, this study provides new insights into new therapeutic methods via inhibiting autophagy.
|
