Cancer-selective therapy of the future: Apoptin and its mechanism of action

Maddika, Subbareddy; Mendoza, Francisco J; Hauff, Kristin; Zamzow, Christina R.; Paranjothy, Ted; Łos, Marek

doi:10.4161/cbt.5.1.2400

Cited by 74 publications

(59 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptosis also plays an important role in the embryonic development, during the regulation of the immune response and in tissue homeostasis Khosravi-Far and Esposti, 2004;Okada and Mak, 2004;Oliver and Vallette, 2005). The induction of programmed cell death occurs via two major pathways: the death receptor-dependent (extrinsic) pathway through TNFfamily ligands, or via the mitochondrial (intrinsic) pathway induced by different factors such as UV radiation, chemotherapeutics, free radicals or DNA damage (Brouckaert et al, 2005;Los et al, 1995;Maddika et al, 2006). The induction of apoptosis leads to cell blebbing, exposure of phosphatidylserine at the cell surface, reduction of cell size, shrinkage of the cell core, DNA condensation and the formation of apoptotic bodies (Darzynkiewicz et al, 1997;Khosravi-Far and Esposti, 2004).…”

Section: General Introduction: Linking Cell Cycle Cell Survival and mentioning

confidence: 99%

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Maddika¹,

Ande²,

Panigrahi³

et al. 2007

Drug Resistance Updates

408

302

View full text Add to dashboard Cite

The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic regulatory circuits. This review highlights some of the connections between opposite-acting pathways. Thus, we discuss the role of cyclins in the apoptotic process, and in the regulation of cell proliferation. CDKs and their inhibitors like the INK4-family (p16 Ink4a , p15 Ink4b , p18 Ink4c , p19 Ink4d ), and the Cip1/Waf1/Kip1-2-family (p21 Cip1/Waf1 , p27 Kip1 , p57 Kip2 ) are shown both in the context of proliferation regulators and as contributors to the apoptotic machinery. Bcl2-family members (i.e. Bcl2, Bcl-X L Mcl-1 L ; Bax, Bok/Mtd, Bak, and Bcl-X S ; Bad, Bid, Bim EL , Bmf, Mcl-1 S ) are highlighted both for their apoptosis-regulating capacity and also for their effect on the cell cycle progression. The PI3-K/Akt cell survival pathway is shown as regulator of cell metabolism and cell survival, but examples are also provided where aberrant activity of the pathway may contribute to the induction of apoptosis. Myc/Mad/Max proteins are shown both as a powerful S-phase driving complex and as apoptosis-sensitizers. We also discuss multifunctional proteins like p53 and Rb (RBL1/p107, RBL2/p130) both in the context of G 1 -S transition and as apoptotic triggers. Finally, we reflect on novel therapeutic approaches that would involve redirecting over-active survival and proliferation pathways towards induction of apoptosis in cancer cells.

show abstract

Section: General Introduction: Linking Cell Cycle Cell Survival and mentioning

confidence: 99%

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Maddika¹,

Ande²,

Panigrahi³

et al. 2007

Drug Resistance Updates

408

302

View full text Add to dashboard Cite

show abstract

“…Such activities have been demonstrated for the adenovirusderived E4orf4, the parvovirus H1 protein NS1 and chicken anemia virus-derived apoptin (Guelen et al, 2004;Maddika et al, 2005;Maddika et al, 2006;Rohn and Noteborn, 2004) (Table 1). During natural infection, these proteins orchestrate the cytolytic events that are requisite for successful spreading of the virus.…”

Section: Strategies To Selectively Kill Tumor Cellsmentioning

confidence: 78%

“…Finally, apoptin induces apoptosis in a wide variety of human cancer cell lines via classical apoptotic pathways (Rohn and Noteborn, 2004;Maddika et al, 2005Maddika et al, , 2006Backendorf et al, 2008). Several independent in vivo analyses using human xenografted tumors have proven that administration of apoptin, as well as its recombinant version protein transduction domain 4 (PTD4)-apoptin, results in a significant reduction of tumor growth without major side effects (Peng et al, 2007;Sun et al, 2009).…”

Section: Strategies To Selectively Kill Tumor Cellsmentioning

confidence: 99%

Towards novel paradigms for cancer therapy

et al. 2010

View full text Add to dashboard Cite

Cancer is a complex progressive multistep disorder that results from the accumulation of genetic and epigenetic abnormalities, which lead to the transformation of normal cells into malignant derivatives. Despite enormous progress in the understanding of cancer biology including the decryption of multiple regulatory networks governing cell growth and death, and despite the possibility of analyzing (epi)genetic deregulation at the genome-wide scale, cancertargeted therapy is still the exception. In fact, to date there are still far too few examples of therapies leading to cure; treatment-derived toxicity is a major issue, and cancer remains to be one of the largest causes of death worldwide. The purpose of this review is to discuss the state of the art of cancer therapy with respect to the key issue of any treatment, namely its target selectivity. Therefore, we recapitulate and discuss current concepts and therapies targeting tumorspecific features, including oncofusion proteins, aberrant kinase activities and epigenetic tumor makeup. We analyze strategies designed to induce tumor-selective death such as the use of oncolytic virus, tumoricidal proteins (NS1, Eorf4, apoptin, HAMLET (human a-lactalbumin made lethal to tumor cells)) and activation of signaling pathways involved in tumor surveillance. We emphasize the potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, an essential component of the evolutionary developed defense systems that eradicate malignant cells. Finally, we discuss the necessity of targeting tumor-initiating cells (TICs) to avoid relapse and increase the chances of complete remission, and describe emerging concepts that might provide novel avenues for cancer therapy.

show abstract

“…8,9 Therefore, E4orf4 is potentially useful in anticancer therapies. 23 In the last decade, researches were mostly concentrated on the study of the mechanism of E4orf4 selectively toward cancer cells using in vitro gene transfection methods. Mitrus et al 17 gave the first report in which therapeutic DNA containing E4orf4 gene was administered via electroporation directly into the murine B16 (F10) tumors.…”

Section: Discussionmentioning

confidence: 99%

Fusion protein of adenovirus E4orf4 and human epidermal growth factor inhibits tumor cell growth

Zhou

Chen

Xie

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

Adenovirus early region 4 open reading frame 4 (E4orf4) protein is a novel cell death factor that selectively induces apoptosis in cancer cells. This study evaluated tumor inhibitory effects of a protein made by fusion E4orf4 and human epidermal growth factor (EGF). EGF was used to ensure the selective targeting of EGF receptor (EGFR)-overexpressing tumor cells. Results showed that EGF-E4orf4 stimulated EGFR phosphorylation in a time-and dose-dependent manner. Confocal microscopy analysis showed both EGF-E4orf4 and EGF could be internalized via EGFR but they had different intercellular trafficking pathways. In vitro study showed that EGF-E4orf4 significantly inhibited the proliferation of BGC823 and in vivo study showed EGF-E4orf4 suppressed tumor growth in a dose-dependent fashion with an inhibition rate of 79% for MDA-MB-231 and 49% for BGC 823 (p < 0.05). No toxic effects were observed in the nude mice with a dose as high as 10 mg/kg of EGF-E4orf4. These results indicated that EGFE4orf4 could be a potential drug for cancer therapy. ' 2009 UICC

show abstract

Cancer-selective therapy of the future: Apoptin and its mechanism of action

Cited by 74 publications

References 58 publications

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Towards novel paradigms for cancer therapy

Fusion protein of adenovirus E4orf4 and human epidermal growth factor inhibits tumor cell growth

Contact Info

Product

Resources

About