- |||||||||| Journal: Autophagic degradation of MVBs in LSECs promotes Aldosterone induced-HSCs activation. (Pubmed Central) - Jun 18, 2023
This autophagy leads to the degradation of MVBs in LSECs, resulting in a reduction of the number of EVs and miR-342-5p content within EVs. This reduction ultimately leads to a diminished inhibitory signal transmitted to HSCs, thereby activating HSCs and promoting the development of liver fibrosis.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: SPINK1 contributes to proliferation and clonal formation of HT29 cells through Beclin1 associated enhanced autophagy. (Pubmed Central) - Jun 16, 2023 Chloroquine (CQ) significantly decreased the level of autophagy in both control and SPINK1-OE HT29 cells...Collectively, SPINK1-promoted proliferation and clonal formation of HT29 cells were closely associated with Beclin1 associated enhanced autophagy. The above findings would open a new window for probing the role of SPINK1-related autophagic signaling in the pathogenesis of CRC.
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Journal, IO biomarker: Long Noncoding RNA MIATNB Regulates Hyperosmotic Stress-induced Corneal Epithelial Cell Injury by Inhibiting Autophagy in Dry Eye Disease. (Pubmed Central) - Jun 16, 2023 RT-qPCR was performed to assess the expression of dry eye related LC3B, ATG16L, BECN1, ATG1, ATG7, ATG13, ATG5, ATG10, and ATG101 mRNAs and western blot analysis of LC3B and P62 and RFP -GFP-tagged LC3...Chloroquine (CQ) was used to inhibit autophagy pharmacologically...MIATNB plays a vital role in dry eye pathogenesis and serves as a bridge between autophagy and apoptosis. Targeting MIATNB for DED treatment should be further evaluated.
- |||||||||| Ibrance (palbociclib) / Pfizer
Journal: Palbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagy. (Pubmed Central) - Jun 14, 2023 Finally, the SASP varied upon inhibiting mTORC1, or upon the combined inhibition of mTORC1 and autophagy, generating diverse responses in cell proliferation, invasion, and migration of non-senescent tumorigenic cells. Overall, variations in the SASP of Palbociclib-driven senescent cells with the concomitant inhibition of mTORC1 seem to depend on autophagy.
- |||||||||| Journal: SLIT2/ROBO1 signaling suppresses mTORC1 for organelle control and bacterial killing. (Pubmed Central) - Jun 13, 2023
We also show that impediment of auto/paracrine SLIT-ROBO signaling axis in cancer cells leads to hyperactivation of mTORC1 and inhibition of autophagy. Together, these findings elucidate a central role of chemorepellent SLIT2 in the regulation of mTORC1 activity with important implications for innate immunity and cancer cell survival.
- |||||||||| Characterization of the molecular mechanism of autophagy inhibition by HER2 (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_1285;
Such correlation was even more prominent when protein levels were analyzed by RPPA, suggesting that patients with decreased protein X levels may have an induced autophagy. Furthermore, these patients with low protein X and p62 presented a better overall and progression-free survival than those with high levels of both proteins.ConclusionTaken together, our data suggest that a new BECN1-interacting protein mediates the binding of HER2 to BECN1and represents a potential new regulator of autophagy activity and tumour growth.
- |||||||||| picropodophyllin (AXL1717) / Axelar
Combined inhibition of Insulin Growth Factor-1 Receptors and Autophagy to hinder Colorectal Cancer Metastasis: A Novel Therapeutic Approach (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_1130; We compared the autophagy genes expression, migration (wound healing assay) as well as the expression epithelial-mesenchymal transition markers; E-cadherin, N-cadherin, Snail1 and Zeb1 (Western Blotting) in different cell lines [isogenic cell lines, HCT116, LOVO, SKCO1, treated with IGF-1, knocked down for IGFR or using its inhibitor (picropodophyllin; PPP)].Results and DiscussionsThere was an increase in basal autophagosome formation as well as autophagy flux subsequent to IGF-1 treatment; revealed by ATG5 and ATG7 increased levels (WB (, whereas suppressed by PPP...Combined suppression of IGF-1 and autophagy represents a potential therapeutic modality for fighting metastasis in advanced colorectal cancer. *The study is funded by MBRU-Al-Mahmeed Research Award (ALM#1914).
- |||||||||| telmisartan / Generic mfg.
Telmisartan derivatives induce mitochondrial fission and modulate autophagy in melanoma cell lines (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_838; Reduced HMOX1 expression achieved better anticancer effects concomitantly with pimozide treatment. We selected 3 new derivatives with the best cytotoxic effects against A375 and vemurafenib-resistant A375 (A375R) human melanoma cells to further investigate the mechanisms by which derivatives lead to cell death.Material and MethodsThe cytotoxicity of 3 new derivatives and telmisartan were examined using an MTT test after 72 h of treatment...The autophagic flux was examined with fluorescent microscopy of LC3 upon treatment with telmisartan derivatives alone and in combination with known autophagy inducer and inhibitor
- |||||||||| Mekinist (trametinib) / Novartis, Sutent (sunitinib) / Pfizer
Mitochondrial fission mediator DRP1 is modulated by chemotherapy but does not mediate drug resistance in pediatric sarcomas. (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_675; In contrast with reports in carcinomas, reduced levels of DRP1 resulted in a 2.3-fold increased resistance to cisplatin in rhabdomyosarcoma RD cells.ConclusionOverall, our results revealed that mitochondrial fission mediator DRP1 is modulated by exposure to chemotherapy but does not mediate drug resistance in osteosarcoma and rhabdomyosarcoma. Our findings point to a potential compensatory DRP1-independent fission mechanisms which require further investigation in pediatric sarcomas.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Simultaneous apoptosis and autophagy occurrence in colorectal cancer cells by the synergism of doxorubicin and tocotrienol (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_609; Besides, the combined treatment induced an enhanced autophagy in the treated cancer cells as evidenced by the formations of acidic vacuolar organelles, phagophores and autophagosomes, as well as increments of monodansylcadaverine intensity and microtubule-associated protein 1A/1B light chain 3 (LC3)-II expression. The involvement of autophagic cell death is further confirmed when the application of autophagy inhibitors, namely 3-methyladenine and bafilomycin A1 successfully reverted cell death.ConclusionOverall, current findings supported that T3+Dox combined treatment exerted both apoptosis and autophagy in Caco-2 and SW48 cells, where these multitargeted actions are highly imperative for treating the invasive type of CRC in the future.
- |||||||||| Development of novel nanoparticles to treat breast cancer by targeting autophagy (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_597;
ConclusionHere, we target not only the tumor-specific pathways but also cell metabolism through targeting autophagy. We developed non-toxic, bio-compatible SPION-based AGO2 protein containing theranostic nanoparticles that are efficiently used as innovative gene therapy tools for targeted cancer therapy.
- |||||||||| sirolimus / Generic mfg., gemcitabine / Generic mfg.
Establishment of isoliquiritigenin as a novel autophagy-ferritinophagy regulator in pancreatic cancer adjuvant chemotherapy (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_525; Moreover, autophagy inducer rapamycin enhanced ISL-evoked cell growth inhibition and promoted apoptosis, while inhibition of autophagosome formation by siAtg5 attenuated ISL-induced apoptosis...Despite the view that ferritinophagy-mediated ferroptosis may contribute to tumor suppression, alternative reports also indicated that elevated ferritinophagy expression signature predicts poor prognosis in PDAC patients while ferroptotic cell death could aggravate pancreatic cancer by reprogramming of tumor immunity. In our study, ISL exhibited reduction of myeloid-derived suppressor cell numbers in both PDAC tumor tissues and the peripheral blood, with concurrent increase in CD4+ and CD8+ T cell numbers, together with attenuation of M2-polarization in tumor-associated macrophages.ConclusionOur findings have suggested that ISL can be established as a novel autophagy-ferritinophagy regulator in adjuvant chemotherapy of pancreatic cancer.
- |||||||||| Review, Journal: SGLT2 inhibitors and autophagy in diabetes. (Pubmed Central) - Jun 12, 2023
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of newly introduced antidiabetic drugs that achieve normoglycemia through causing overt glycosuria. There is evidence that these drugs may have pleiotropic extra-glycemic benefits, but their effect on the autophagy process is unclear; therefore, this review was undertaken to clarify the possible effects of SGLT2is on autophagy.
- |||||||||| Journal: The AMPK-dependent inhibition of autophagy plays a crucial role in protecting photoreceptor from photooxidative injury. (Pubmed Central) - Jun 11, 2023
Neuroprotective effects caused by the AMPK-dependent inhibition of autophagy were also verified with a retinal light injured mouse model in vivo. Overall, our findings demonstrated that AMPK / mTOR pathway could inhibit autophagy through AMPK-dependent inhibition of autophagy to significantly protect the photoreceptors from photooxidative injury, which may aid to further develop novel targeted retinal neuroprotective drugs.
- |||||||||| Journal: SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis. (Pubmed Central) - Jun 9, 2023
Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD. The SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC.
- |||||||||| Quinamed (amonafide) / Teva
Journal: Amonafide Induces HUVEC Senescence by Inhibiting Autophagy. (Pubmed Central) - Jun 9, 2023 Amonafide-induced cellular aging by inhibiting autophagy and activating the mTOR pathway. The findings may offer new strategies for managing adverse reactions to amonafide.
- |||||||||| Journal: NFATc1-mediated expression of SLC7A11 drives sensitivity to TXNRD1 inhibitors in osteoclast precursors. (Pubmed Central) - Jun 7, 2023
Together, our findings demonstrate that NFATc1-mediated upregulation of SLC7A11 induces targetable metabolic sensitivity to TXNRD1 inhibitors during osteoclast differentiation. Moreover, we innovatively suggest that TXNRD1 inhibitors, a classic drug for osteoclast-related diseases, selectively kill pre-OCs by inducing intracellular cystine accumulation and subsequent disulfidptosis.
- |||||||||| sirolimus / Generic mfg.
Journal: Resveratrol inhibits autophagy against myocardial ischemia-reperfusion injury through the DJ-1/MEKK1/JNK pathway. (Pubmed Central) - Jun 5, 2023 Notably, the autophagic agonist rapamycin (RAPA) eliminated RES-induced cardioprotective effects...However, the lentiviral shDJ-1 and JNK agonist anisomycin disrupted the effects of RES. In summary, RES could inhibit autophagy against myocardial ischemia-reperfusion injury through DJ-1 modulation of the MEKK1/JNK pathway, providing a novel therapeutic strategy for cardiac homeostasis.
- |||||||||| epirubicin / Generic mfg.
Journal: TCF12 regulates exosome release from epirubicin-treated CAFs to promote ER+ breast cancer cell chemoresistance. (Pubmed Central) - Jun 5, 2023 Furthermore, exosome secreted from EPI-treated CAFs not only prevented ROS accumulation in CAFs but also upregulated the CXCR4 and c-Myc protein levels in recipient ER+ breast cancer cells, thus promoting EPI resistance of tumor cells. Together, the current study provides novel insights into the role of stressed CAFs in promoting tumor chemoresistance and reveal a new function of TCF12 in regulating autophagy impairment and exosome release.
- |||||||||| Journal, IO biomarker: IL-17A inhibits the degradation of RANKL in osteoblasts by inhibiting BCL2-Beclin1-autophagy signaling. (Pubmed Central) - Jun 5, 2023
Importantly, the supernatant from osteoblasts treated with 50 ng/mL of IL-17A made osteoclast precursors (OCPs) form larger osteoclasts, which was reversed by BCL2 knockdown in osteoblasts. In conclusion, high levels of IL-17A prevent the degradation of RANKL by inhibiting BCL2-Beclin1-autophagy activation signal transduction in osteoblasts, thereby indirectly promoting osteoclastogenesis.
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