Why Sick Cells Produce Tumors: The Protective Role of Autophagy

Mathew, Robin; White, Eileen

doi:10.4161/auto.4605

Cited by 61 publications

(46 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Resistance to apoptosis improves the genetic instability of the cell (e.g., DNA-damage foci, aneuploidy, supernumerary centrosome) (38) and is an essential step in tumorigenesis (39) allowing the cell to escape from immunosurveillance (40). High incidence of lymphomas and atypical malignancies are a hallmark of renal transplant recipients (41).…”

Section: Discussionmentioning

confidence: 99%

The Immunosuppressor Mycophenolic Acid Kills Activated Lymphocytes by Inducing a Nonclassical Actin-Dependent Necrotic Signal

Chaigne-Delalande

Guidicelli

Couzi

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Mycophenolate mofetil (MMF) is an immunosuppressive agent used in transplantation. Over the last decade, MMF has also emerged as an alternative therapeutic regimen for autoimmune diseases, mainly for patients refractory to other therapies. The active compound of MMF, mycophenolic acid (MPA), depletes the intracellular pool of guanosine tri-phosphate through inosine monophosphate dehydrogenase blockade. The molecular mechanism involved in the elimination of T and B lymphocytes upon inhibition of inosine monophosphate dehydrogenase remains elusive. In this study, we showed that in contrast to the immunosuppressors azathioprine, cyclosporin A, and tacrolimus, MPA killed lymphocytes through the activation of a caspase-independent necrotic signal. Furthermore, the MPA-mediated necrotic signal relied on the transmission of a novel intracellular signal involving Rho-GTPase Cdc42 activity and actin polymerization. In addition to its medical interest, this study sheds light on a novel and atypical molecular mechanism leading to necrotic cell death.

show abstract

Section: Discussionmentioning

confidence: 99%

The Immunosuppressor Mycophenolic Acid Kills Activated Lymphocytes by Inducing a Nonclassical Actin-Dependent Necrotic Signal

Chaigne-Delalande

Guidicelli

Couzi

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…81 Although autophagy seems to protect cells against cell death under oxidative stress, extended autophagy can induce cell death in several cases, such as precancerous cells. 13,[85][86][87][88] Recent studies suggest a potential link between ROS regulation and autophagic processes, because agents capable of inducing ROS formation play a crucial role in the induction of autophagy in embryonic kidney HEK293 cells, human fibroblast HT1080 cells, and human lung cancer cells. 84,89,90 For instance, platinum-based therapy and epigallocatechin gallate-mediated cell death may also depend on the generation of ROS either directly or indirectly.…”

Section: Combination Of Cis and Rgo-agnps Induces Accumulation Of Autmentioning

confidence: 99%

Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

Yuan¹,

Gurunathan²

2017

IJN

111

View full text Add to dashboard Cite

Background Cisplatin (Cis) is a widely used chemotherapeutic drug for treating a variety of cancers, due to its ability to induce cell death in cancer cells significantly. Recently, graphene and its modified nanocomposites have gained much interest in cancer therapy, due to their unique physicochemical properties. The objective of this study was to investigate the combination effect of Cis and a reduced graphene oxide–silver nanoparticle nanocomposite (rGO-AgNPs) in human cervical cancer (HeLa) cells. Materials and methods We synthesized AgNPs, rGO, and rGO-AgNP nanocomposites using C-phycocyanin. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer properties of the Cis, rGO-AgNPs, and combination of Cis and rGO-AgNPs were evaluated using a series of cellular assays, such as cell viability, cell proliferation, LDH leakage, reactive oxygen species generation, and cellular levels of oxidative and antioxidative stress markers such as malondialdehyde, glutathione, SOD, and CAT. The expression of proapoptotic, antiapoptotic, and autophagy genes were measured using real-time reverse-transcription polymerase chain reaction. Results The synthesized AgNPs were well dispersed, homogeneous, and spherical, with an average size of 10 nm and uniformly distributed on graphene sheets. Cis, GO, rGO, AgNPs, and rGO-AgNPs inhibited cell viability in a dose-dependent manner. The combination of Cis and rGO-AgNPs showed significant effects on cell proliferation, cytotoxicity, and apoptosis. The combination of Cis and rGO-AgNPs had more pronounced effects on the expression of apoptotic and autophagy genes, and also significantly induced the accumulation of autophagosomes and autophagolysosomes, which was associated with the generation of reactive oxygen species. Conclusion Our findings substantiated rGO-AgNPs strongly potentiating Cis-induced cytotoxicity, apoptosis, and autophagy in HeLa cells, and hence rGO-AgNPs could be potentially applied to cervical cancer treatment as a powerful synergistic agent with Cis or any other chemotherapeutic agents.

show abstract

“…On the other hand, one cannot ignore the abundant evidence supporting autophagy as a tumor suppressive mechanism during cancer progression. 18,20,21 Accordingly, detachment-induced autophagy may have yet undiscovered tumor suppressive functions; thus, the cellular consequences of autophagy inhibition during anoikis, both positive and negative, must be further delineated prior to its pursuit as a therapeutic strategy to kill detached tumor cells. As glandular epithelium develops, a population of centrally located cells is cleared to form a lumen.…”

Section: Exploiting Autophagy Against Detached Tumor Cellsmentioning

confidence: 99%

Detachment-induced autophagy duringanoikisand lumen formation in epithelial acini

Debnath

2008

Autophagy

View full text Add to dashboard Cite

The individual units (called acini) comprising glandular epithelium possess a hollow lumen that is filled in early epithelial cancers. While investigating the generation of this hollow lumen using an in vitro three-dimensional (3D) epithelial cell culture model, we observed extensive autophagy in dying cells during lumen formation, and thus, proposed that excessive self-eating may promote cell death in the lumen. However, we now reassess this hypothesis. Because cells in the lumen die due to extracellular matrix (ECM) deprivation (anoikis), we tested if autophagy is regulated by ECM detachment. We discovered that detachment strongly induces autophagy in epithelial cells, even when apoptosis is inhibited by Bcl-2 expression. RNAi-mediated depletion of autophagy-related (ATG) genes inhibits detachment-induced autophagy, resulting in increased apoptosis and reduced clonogenic recovery following anoikis. Similarly, during 3D morphogenesis, ATG-depletion enhances luminal apoptosis and fails to elicit long-term luminal survival and filling, even when combined with apoptotic inhibition. Thus, autophagy promotes epithelial cell survival during anoikis. These results broach the possibility that autophagy contributes to the survival of tumor cells lacking appropriate matrix contact, either during early carcinoma formation or in the later stages of dissemination and metastasis.

show abstract

Why Sick Cells Produce Tumors: The Protective Role of Autophagy

Cited by 61 publications

References 35 publications

The Immunosuppressor Mycophenolic Acid Kills Activated Lymphocytes by Inducing a Nonclassical Actin-Dependent Necrotic Signal

The Immunosuppressor Mycophenolic Acid Kills Activated Lymphocytes by Inducing a Nonclassical Actin-Dependent Necrotic Signal

Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

Detachment-induced autophagy duringanoikisand lumen formation in epithelial acini

Contact Info

Product

Resources

About

Why Sick Cells Produce Tumors: The Protective Role of Autophagy

Cited by 61 publications

References 35 publications

The Immunosuppressor Mycophenolic Acid Kills Activated Lymphocytes by Inducing a Nonclassical Actin-Dependent Necrotic Signal

The Immunosuppressor Mycophenolic Acid Kills Activated Lymphocytes by Inducing a Nonclassical Actin-Dependent Necrotic Signal

Combination of graphene oxide&ndash;silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

Detachment-induced autophagy duringanoikisand lumen formation in epithelial acini

Contact Info

Product

Resources

About

Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells