Apoptosis and Molecular Targeting Therapy in Cancer

Hassan, Mohamed K.; Watari, Hidemichi; Abu-Almaaty, Ali H.; Ohba, Yusuke; Sakuragi, Noriaki

doi:10.1155/2014/150845

Cited by 903 publications

(719 citation statements)

References 268 publications

(315 reference statements)

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“…In contrast to the anti-apoptotic role of c-FLIP at high levels of expression, c-FLIPL has been demonstrated to induce apoptosis at low and more physiologically relevant expression levels by recruiting at the DISC to increase caspase-8 activation (Chang et al, 2002). In spite of the known dual function of c-FLIPL as a pro-or anti-apoptotic factor in normal tissues, c-FLIPL has usually been identified as taking action as a fundamental negative regulator of apoptosis in human cancer cells (Hassan et al, 2014). C-FLIP is a transcriptional target of a number of transcription factors.…”

Section: Role Of Apoptosis In Cancermentioning

confidence: 99%

“…Some members of the SRTF superfamily that can downregulate the expression of Bcl-2 or Bcl-xL are some small molecule drugs that modulate the activity of retinoic acid receptors (RAR), retinoid X receptors (RXR), PPAR, and vitamin D receptors (VDR) in specific types of cancer and leukemia cells (Hassan et al, 2014). For instance, Troglitazoneor Δ2-TG, a potent PPAR agonist, can inhibit the anti-apoptotic functions of Bcl-xL and Bcl-2 and cause caspase-dependent apoptosis via caspase-9 activation (Shiau et al, 2005;Grillier-Vuissoz and Isabelle, 2012).…”

Section: Cont) Preclinical and Clinical Trials Of Therapeutic Agentsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

455

299

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Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

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Section: Role Of Apoptosis In Cancermentioning

confidence: 99%

Section: Cont) Preclinical and Clinical Trials Of Therapeutic Agentsmentioning

confidence: 99%

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

455

299

View full text Add to dashboard Cite

show abstract

“…In order to promote phagocytosis of apoptotic cells by macrophages, apoptotic cells present specific membrane morphologies to activate this process. One of these changes is the translocation of phosphatydilserine from the inside of the cell to the outer surface, followed by membrane blebbing and small vesicles called apoptotic bodies (5). In the early stages of apoptosis, caspases are activated in order to initiate and accomplish the cleavage of essential cellular components.…”

Section: Targets Of Mdr Cancer Cellsmentioning

confidence: 99%

Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype

Amaral

Spengler

Molnár

2016

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Abstract. The focus of this mini-review is to identify non-toxic compounds isolated from natural sources (plants) that exhibit specific activity against efflux pumps of specific multidrugresistant (MDR) cancer cell lines, inhibit proliferation of the MDR cancer cell lines and inhibit the activity of overexpressed efflux pumps of the MDR cancer cell line.Therapy of cancer, if not completely effective, results in the overexpression of genes that code for efflux pumps that extrude the noxious agent (anticancer drug) before it reaches its intended target of the cancer cell (1). The overexpressed efflux pump renders the cancer cell immune to not only the initial drug used in therapy but to a wide range of unrelated noxious compounds (1). The arising of this multidrugresistant (MDR) phenotype makes therapy highly problematic and the end result is that the patient succumbs to the disease (1). Therefore, it is the consensus of many that therapy of MDR cancer may succeed if the responsible efflux pump is inhibited from its activity, therefore, affording the increased concentration of anticancer drug to a level consistent with its toxic targeted action needed to kill the cancer cell. To this extent, over 100,000 synthetic compounds for activity against the known efflux pumps of cancer cell types have been screened by the National Cancer Institute (USA) and, to date, not a single inhibitor has found its way toward successful therapy of MDR cancer. In fact, because normal counter type cells have a fully functional efflux pump, albeit at a much lower level of activity, clinical trials with selected efflux pump inhibitors have produced high toxicity and even death.During the past two decades, traditional medicine has become a source for the identification of plants that harbor compounds that may have important potential for the therapy of cancer. With respect to the laboratory of one of the authors of this mini-review (JM), literally, hundreds of plants have been studied for their activity against specific targets of the cancer cell and it is the focus of this mini-review to identify selected compounds that have no toxicity at the level of their in vitro study and which have activity against proliferation or induction of the apoptotic mechanism or the efflux pump responsible for the phenotype of the MDR cancer cell. Targets of MDR Cancer CellsProliferation. Proliferation is affected by many drugs and, although the search for non-toxic compounds that inhibit proliferation was initiated more than 60 years ago, remains the focus of most studies; however, the inhibition of proliferation by compounds isolated from natural sources will not be discussed here at the level of its mechanism. Rather, suffice to say that our observations for antiproliferative activity as presented in the text remain, for the 5665

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“…In recent years, a lot of research has been conducted to the synthesis of potential anticancer drugs (2)(3)(4). A successful anticancer drug should kill or inactivate cancer cells without causing excessive damage to normal cells (5,6). Discovering of cisplatin by Rosenberg in the 1970s, platinum complexes became one of most commonly explored class of cytostatics in anticancer chemotherapy, but only a few are in worldwide clinical practice use or in clinical trials (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…

ABSTRACT

SAŽETAK

Šest kompleksa zlata(III) sa cikloheksil-funkcionalizovanim estrima etilendiamin-N,N'-diacetata, opšte formule [AuCl 2 {(S,S)-R 2 eddch}]PF 6 , ((S,S)-eddch = (S,S)-etilendiamin-N,N'-di-2-(3-cicloheksil)propanoat, R = Me, Et, n-Pr, n-Bu, i-Bu, i-Am, 1-6), ispitivano je na humanim ćelijskim linijama malignog melanoma Fem-x, karcinoma debelog creva LS174T, karcinoma pluća A549 kao i normalnim ćeli-jama MRC-5 (fetalni plućni fi broblast) korišćenjem

…”

mentioning

confidence: 99%

Antiproliferative Activity of Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N’-Diacetate

Pantelić

Stanojković

Zmejkovski

et al. 2017

Serbian Journal of Experimental and Clinical Research

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Six gold(III) complexes with esters of cyclohexyl-functionalized ethylenediamine-N,N'-diacetate, general formula [AuCl 2 {(S,S)-R 2 eddch}]PF 6 , [(S,S)-eddch = (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate, R = Me, Et,[1][2][3][4][5][6], respectively], were tested against cancer cell lines such as human melanoma Fem-x, human colon carcinoma LS174T and non-small cell lung carcinoma A549 as well as a non-cancerous human embryonic lung fi broblasts [3][4] SAŽETAK Šest kompleksa zlata(III) sa cikloheksil-funkcionalizovanim estrima etilendiamin-N,N'-diacetata, opšte formule [AuCl 2 {(S,S)-R 2 eddch}]PF 6 , ((S,S)-eddch = (S,S)-etilendiamin-N,N'-di-2-(3-cicloheksil)propanoat, R = Me, Et, n-Pr, n-Bu, i-Bu, i-Am, 1-6), ispitivano je na humanim ćelijskim linijama malignog melanoma Fem-x, karcinoma debelog creva LS174T, karcinoma pluća A549 kao i normalnim ćeli-jama MRC-5 (fetalni plućni fi broblast) korišćenjem

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Apoptosis and Molecular Targeting Therapy in Cancer

Cited by 903 publications

References 268 publications

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype

Antiproliferative Activity of Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N’-Diacetate

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