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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
It is a self-digestion process, which is also another source of cell death. It is the process where it removes and degrades the damaged cellular constituents by which a small portion of cellular components are isolated from the rest of the cell to form a double layered vesicle called autophagosome. Autophagosome further fuses with lysosome having low pH (acidic) and later endosome to form autolysosome. When autophagy and lysosome degradation is disturbed, Cathespin B is released from lysosome to trigger mitochondrial permeabalization and caspase activation. Cathespin D is translocated from lysosome to cytosol, which is responsible for Bax activation and apoptotic induced factor release. In addition, caspase cleave autophagy relative proteins, such as Beclin1, Bcl-2, P53, and UV-irradiation resistance gene (UVRAG), are several tumor proteins that regulate autophagy.
Role of Vitamin D and Antioxidant Functional Foods in the Prevention and Treatment of Alzheimer’s Disease Pathology
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Mediators of apoptosis involved in AD disease include c-jun (the protein encoded by the JUN gene that forms the AP-1 early response transcription factor), BCL2 (apoptosis regulator B-cell lymphoma 2 protein), and BCL-xL (B-cell lymphoma-extra-large, apoptosis-related transmembrane molecule in the mitochondria). A decrease in BLC2 is observed in NFT and an increase in Bax (apoptosis regulator) is observed in neurons of some microglia in AD brains. Some of the caspases involved include caspases 3/6 and 9 which can be associated with misfolded tau. Even though apoptosis is a contributor to the cell death observed in AD, it is not confirmed that it is responsible for all death observed with this disease. Apoptosis may not be significantly increased in AD animal disease models. In humans, necrosis is also an important contributor to AD cell death. One mechanism thought to be relevant in neuronal loss synaptic loss is nonapoptotic sublethal caspase activation in the dendrite’s axons. Inhibition of apoptosis protein and proteasome activity may have a role in leading the cell fat into a nonapoptotic pathway. Beclin-1 (protein encoded by the BECN1 gene) expression is decreased in human brains during aging and reduces beta-amyloid pathology in APP mice.
Mitochondrial Dysfunction, Immune Systems, Their Diseases, and Possible Treatments
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Elise Jacquin, Eric Hervouet, Michaël Boyer-Guittaut
Chronic inflammation has been described in numerous cases as a trigger to induce more aggressive pathologies. It is for example the case in colitis-associated cancer (CAC) in which inflammasome activity is altered leading to continuous inflammation. A new small molecule, Andrographolide (Andro), has been described to inhibit NRLP3-inflammasome activity in macrophages and the release of pro-inflammatory cytokine IL-1β, and to attenuate colitis and tumor growth.79 More interestingly, Andro has been shown to induce mitophagy in macrophages and therefore to inhibit the accumulation of damaged mitochondria presenting mitochondrial membrane potential collapse. This effect was confirmed to be mitophagy-specific since Becn1 knockdown as well as autophagy inhibitors inhibited this effect. This result demonstrated that Andro inhibited NRLP3-inflammasome activity by degrading damaged mitochondria and then leading to the attenuation of CAC.
Roles of Beclin1 protein expression in cervical cancer: a meta-analysis and bioinformatics analysis
Published in Journal of Obstetrics and Gynaecology, 2022
Guan-Ying Ma, Shuai Shi, Hong-Yan Ma, Zhi-Gang Zhang
Beclin1 is a tumour suppressor gene, so the higher the expression level of Beclin1, the better the prognosis of tumours, and plays a significant part in the development of tumour diseases (Stang 2010; Wang J et al. 2017; Wang YY et al. 2017). Beclin1 is a gene that positively regulates autophagy and can regulate the process of autophagy. Beclin1 suppresses tumours primarily by blocking mutations in cancer-related genes. It can induce autophagy apoptosis of tumour cells. It can inhibit the angiogenesis of tumour tissue (Duan and Peng 2011). Cheng et al. conducted an in vitro culture of cervical cancer cells with rectal metastases and found that Beclin1 was able to inhibit the metastasis and invasion of the metastatic cell line HeLa cells, suggesting that the inhibitory effect of Beclin1 on cell proliferation was relevant (Cheng YX et al. 2016). Although there are few studies on Beclin1 expression in cervical cancer at home and abroad, some studies have found that Beclin1 protein expression is decreased in brain tumours, lung cancer, ovarian cancer, breast cancer and endometrioid adenocarcinoma, especially the progression and prognosis of cervical cancer is associated with decreased Beclin1 expression level (Cerit et al. 2018). Studies have shown that the positive rate of Beclin1 in cervical cancer tissues, cervical squamous intraepithelial lesions and normal mucosa increases successively, and Beclin1 gene inhibits the formation and development of cervical cancer, which has a certain correlation with its prognosis (Liu C et al. 2013). This is consistent with the trend of the results of our experimental analysis.
The role of autophagy and mitophagy in cancers
Published in Archives of Physiology and Biochemistry, 2022
Studies have found that Beclin1 is deleted in ovarian, breast and prostate cancers (Gajewska et al.2008), and that the decreased expression of Beclin1 can be observed in brain tumours (Miracco et al.2007) and cervical cancer (Cao and Klionsky 2007). In addition, studies have demonstrated that a lower expression of Beclin1 translates into a higher proliferation potential, and conversely, a higher level of Beclin1 means better prognosis (Koukourakis et al.2010). Furthermore, numerous studies suggest that Beclin1 regulates two types of cell death, namely, autophagy and apoptosis (Djavaheri-Mergny et al.2010, Fu et al.2013). Wirawan et al. (2010) reported that caspase-3, -7 and -8 cleave Beclin1 into Beclin1-C and Beclin1-N, thereby destroying its ability to induce autophagy, while assigning it a new role in activating apoptosis by translocating Beclin1-C to the mitochondrion, where it enhances cytochrome C (cyt C) release.
Triangle collaboration assessment of autophagy, ER stress and hypoxia in leukemogenesis: a bright perspective on the molecular recognition of B-ALL
Published in Archives of Physiology and Biochemistry, 2021
Fatemeh Feizi, Mehdi Allahbakhshian Farsani, Amin Mirzaeian, Vahide Takhviji, Abbas Hajifathali, Mohammad Hossein Mohammadi
Molecular research has been illustrated how an interaction between the BECN1 and up-stream pathways is able to regulate autophagy. As mentioned above, BECN1-dependent autophagy might be tightly regulated by its binding partners, regulator signalling pathways and related transcriptional factors (Helgason et al.2011). In this respect, a number of papers have been shown that hypoxia inducible factor 1 subunit alpha (HIF1A) as a hypoxic transcriptional factor could induce autophagy by up-regulation of BCL2 interacting protein 3 (BNIP3) and BNIP3 Ligand (Füllgrabe et al.2016). The hypoxia-inducible gene BNIP3, as a constitutive component of autophagy, is also the proapoptotic member of the B-cell lymphoma-2 (BCL2) family that could contribute to BECN1-activation through inhibition of the BCL2-activity (Murai et al.2005b). Indeed, BCL2 is a pivotal molecule in the autophagy and apoptosis interaction along with down-regulation performance of the both of them by interacting with the BH3 domain of BECN1 (Nencioni et al.2013). Furthermore, under ER stress, ER to nucleus signalling 1 triggers BCL2-phosphorylation through c-Jun N-terminal kinase 1 (JNK1)/JUN pathway and consequently dissociation of BECN1 from BCL2. Accordingly, proautophagic activity of BECN1 could be increased following BCL2 suppression (Füllgrabe et al.2016). In another pathway, death-associated protein kinase 1 (DAPK1), a tumour suppressor and cell suicide promoter gives rise to BECN1 phosphorylation at the BH3 domain, this in turn induces autophagy (Kang et al.2011).