Induction of Apoptotic Cell Death in Tumor Cells by S100A8/A9 Released from Inflammatory Cells Upon Cellular Activation

Ghavami, Saeid

doi:10.2174/1568014054546326

Cited by 5 publications

(4 citation statements)

References 79 publications

(158 reference statements)

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“…It has been previously reported that treatment of HT29/249 and SW742 cells with S100A8/A9 increases the intracellular level of ROS, and antioxidants reversed the apoptosis-inducing activity of S100A8/A9 [1,42]. This prompted us to investigate the mitochondrial pathway in S100A8/A9-induced cell death using cellular models in which Bcl2 was over-expressed.…”

Section: Discussionmentioning

confidence: 99%

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S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2

Ghavami

Kerkhoff

Chazin

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

109

113

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A complex of two S100 EF-hand calcium-binding proteins S100A8/A9 induces apoptosis in various cells, especially tumor cells. Using several cell lines, we have shown that S100A8/A9-induced cell death is not mediated by the receptor for advanced glycation endproducts (RAGE), a receptor previously demonstrated to engage S100 proteins. Investigation of cell lines either deficient in, or over-expressing components of the death signaling machinery provided insight into the S100A8/A9-mediated cell death pathway. Treatment of cells with S100A8/A9 caused a rapid decrease in the mitochondrial membrane potential (DeltaPsi(m)) and activated Bak, but did not cause release of apoptosis-inducing factor (AIF), endonuclease G (Endo G) or cytochrome c. However, both Smac/DIABLO and Omi/HtrA2 were selectively released into the cytoplasm concomitantly with a decrease in Drp1 expression, which inhibits mitochondrial fission machinery. S100A8/A9 treatment also resulted in decreased expression of the anti-apoptotic proteins Bcl2 and Bcl-X(L), whereas expression of the pro-apoptotic proteins Bax, Bad and BNIP3 was not altered. Over-expression of Bcl2 partially reversed the cytotoxicity of S100A8/A9. Together, these data indicate that S100A8/A9-induced cell death involves Bak, selective release of Smac/DIABLO and Omi/HtrA2 from mitochondria, and modulation of the balance between pro- and anti-apoptotic proteins.

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Section: Discussionmentioning

confidence: 99%

“…S100A8/A9 positive cells, macrophages and polymorphonuclear leukocytes have been shown to accumulate along the invasive margin of a cancer [40]. Moreover, S100A8/A9 is released upon cellular activation [41] and induces apoptosis in malignant cells [1,42].…”

Section: Discussionmentioning

confidence: 99%

S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2

Ghavami

Kerkhoff

Chazin

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

109

113

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“…After systemic administration, toxic side effects were apparent such as the cytokine release syndrome, which is induced in particular by bsAbs containing an anti-CD3 specificity [72,104,150]. Recently there has been a shift towards recruitment of immune system elements and the subsequent induction of apoptosis in consequence of inflammatory processes directed against tumor-associated and TSA contemporarily with death receptors in high amounts [8,74,79]. Theoretically, there is a robust potential to use the death receptors such as Apo--1/Fas/CD95, CD40, CD30, TNF receptors, and TRAIL receptors, not only in cancer, but also in other diseases [43,89].…”

Section: Therapeutic Cell−selective Targeting Of Death Receptors Withmentioning

confidence: 99%

Monoclonal and bispecific antibodies as novel therapeutics

Booy

Johar

Maddika

et al. 2006

Arch. Immunol. Ther. Exp.

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Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. Antibody-based therapy initially entered clinical practice when trastuzumab/Herceptin became the first clinically approved drug against an oncogene product as a well-established blocking reagent for tumors with hyperactivity of epidermal growth factor signaling pathways. In the first part of this review we explain basic terms related to the development of antibody-based drugs, give a brief historic perspective of the field, and also touch on topics such as the "humanization of antibodie" or creation of hybrid antibodies. The second part of the review gives an overview of the clinical usage of bispecific antibodies and antibodies "armed" with cytotoxic agents or enzymes. Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.

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“…Survival of pathologic cells (for example cells which are precancerous, infected or those that could elicit autoimmune response) may contribute to cancer, inflammation and autoimmune diseases. On the other hand, removal of essential cells through excessive apoptosis contributes to the pathogenesis of some degenerative diseases [6][7][8] components is therefore, a useful therapeutic approach to counteract either unwanted survival or death of particular cells associated with certain human diseases [9][10][11]. Most apoptotic pathways converge on the proteolytic activation of members of a family of cysteine aspartyl-specific proteases, (caspases).…”

Section: Introductionmentioning

confidence: 99%

The Immune System, Involvement in Neurodegenerative Diseases, Ageing and Cancer

Booy¹,

Johar²,

Kadkhoda³

et al. 2005

CMCAIAA

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This short review was designed to draw the readership's attention to the following articles in the volume. Instead of providing a full summary of topics such as ageing of the immune system and the role of the immune system in ageing, the role of the immune system in the development of cancer and neurodegenerative diseases, it signalizes these topics and provides links to articles that follow as well as to other available literature. Our intention was to provide a new perspective and strengthen the associations between inflammation, cancer, neuro-degenerative diseases, ageing and autoimmunity. The relationship between inflammation, oxidative stress, apoptosis, neurodegeneration and cancer is already, to a certain extent mirrored by attempts of the pharmacologic industry to cross-apply our current knowledge from these fields to develop new treatment modalities. For instance, strategies that modulate cellular redox potential are being applied to restrain inflammation (antioxidants), or to kill cancer cells (prooxidants). Activation of apoptosis or attenuation of resistance of transformed cells towards cell death induction is perhaps the most promising direction chosen by many pharmaceutical companies to develop new classes of drugs. Furthermore, rapidly developing areas of immunology and virology, combined with the tremendous progress in the field of cancer biology and pharmacogenomics, may lead to the occurrence of an unique treatment, based on anti-cancer viral vectors and even anti-inflammatory strategies, which combine multiple pharmacologic activities in a single bio-molecule.

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Induction of Apoptotic Cell Death in Tumor Cells by S100A8/A9 Released from Inflammatory Cells Upon Cellular Activation

Cited by 5 publications

References 79 publications

S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2

S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2

Monoclonal and bispecific antibodies as novel therapeutics

The Immune System, Involvement in Neurodegenerative Diseases, Ageing and Cancer

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