Sensitizing B- and T- cell Lymphoma Cells to Paclitaxel/Abraxane–Induced Death by AS101 via Inhibition of the VLA-4–IL10–Survivin Axis

Danoch, Hila; Kalechman, Yona; Albeck, Michael; Longo, Dan L.; Sredni, Benjamin

doi:10.1158/1541-7786.mcr-14-0459

Cited by 18 publications

(11 citation statements)

References 46 publications

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“…NF-κB is a transcription factor involved in cell survival and proliferation, which interacts with Op18/stathmin to promote tumor growth and predicts poor prognosis of pancreatic cancer (19)(20)(21). IL-10 is a pleiotropic cytokine which plays a vital role in tumor growth and drug resistance, of which high expression is associated with poor prognosis in tumor patients (22)(23)(24). Bcl-2 is a typical protein against cellular apoptosis induced by chemotherapeutics (25,26).…”

Section: Discussionmentioning

confidence: 99%

Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

Shen

Long

et al. 2017

Oncology Reports

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Taxol (paclitaxel) and vinblastine (VBL) are both efficacious chemotherapeutic agents that target the microtubules of tumor cells, but each functions in a mutual antagonistic manner. Op18/stathmin is a small molecular phosphoprotein which promotes depolymerization of microtubules. Non-small cell lung cancer (NSCLC) NCI-H1299 cells were employed to compare the curative effects of VBL and Taxol and explore the correlation between drug sensitivity and Op18/stathmin signaling. The present study found that VBL obviously promoted cellular apoptosis and initiated activation of caspase 3 and 9, and inhibited cell proliferation and colony formation, as well as cell migration in the NCI-H1299 cells in contrast with Taxol. VBL did not affect the expression of Op18/stathmin, but increased its phosphorylation at all 4 serine sites. Conversely, Taxol mainly decreased the expression of Op18/stathmin and the phosphorylation at Ser25 and Ser63 sites. Silencing of Op18/stathmin by RNA interference (RNAi) led to a great reduction in the differences in the cell proliferation inhibition between VBL and Taxol. VBL treatment notably weakened the expression of PP2A, Bcl-2, NF-κB and interleukin-10 (IL-10) and autocrine IL-10 compared with Taxol; whereas PP2A was substantially increased following Taxol induction. High expression of Op18/stathmin was found to be negatively correlated with the sensitivity of Taxol in the NSCLC cells, but had a minor impact on VBL cytotoxicity. These findings revealed that both VBL and Taxol induce cell apoptosis through Op18/stathmin, but the mechanisms are completely different. VBL is an attractive alternative to the treatment of Taxol-resistant tumors with high expression of Op18/stathmin.

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Section: Discussionmentioning

confidence: 99%

Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

Shen

Long

et al. 2017

Oncology Reports

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“…The anti-inflammatory properties were found crucial for the clinical activities of AS101, including the protective effects of AS101 in autoimmune diseases (15, 16) and in septic mice (17). The same thiol–redox interactions of AS101 enabled it to exert beneficial effects in a variety of tumor models in mice and humans where AS101 had clear antitumor effects (18, 19). Importantly, as part of its activity, AS101 exerts nephroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

The Small Tellurium Compound AS101 Ameliorates Rat Crescentic Glomerulonephritis: Association with Inhibition of Macrophage Caspase-1 Activity via Very Late Antigen-4 Inactivation

et al. 2017

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Crescentic glomerulonephritis (CGN) is the most aggressive form of GN and, if untreated, patients can progress to end-stage renal failure within weeks of presentation. The α4β1 integrin very late antigen-4 (VLA-4) is an adhesion molecule of fundamental importance to the recruitment of leukocytes in inflammation. We addressed the role of VLA-4 in mediating progressive renal injury in a rat model of CGN using a small tellurium compound. AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate]. This compound has been previously shown to uniquely inhibit VLA-4 activity by redox inactivation of adjacent thiols in the exofacial domain of VLA-4. The study shows that administration of AS101 either before or after glomerular basement membrane anti-serum injection ameliorates crescent formation or preserves renal function. This was associated with profound inhibition of critical inflammatory mediators, accompanied by decreased glomerular infiltration of macrophages. Mechanistic studies demonstrated vla-4 inactivation on glomerular macrophages both in vitro and in vivo as well as inhibition of caspase-1 activity. Importantly, this cysteine protease activity modification was dependent on VLA-4 inactivation and was associated with the anti-inflammatory activity of AS101. We propose that inactivation of macrophage VLA-4 by AS101 in vivo results in a decrease of inflammatory cytokines and chemokines produced in the glomeruli of diseased rats, resulting in decreased further macrophage recruitment and decreased extracellular matrix expansion. Thus, AS101, which is currently in clinical trials for other indications, might be beneficial for treatment of CGN.

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“…A combined treatment of rituximab and YM155 was shown to reduce tumor growth more effectively than monotherapy (Kita et al, 2012). In B and T cell lymphoma cells, BIRC5 abrogation using the non-toxic tellurium compound, AS101, has overcome chemoresistance, sensitizing these cells to paclitaxel (Danoch et al, 2015). BIRC5 expression presented anti-apoptotic functions and is regulated by NF-κB and PI3K/AKT signaling pathways in nasal NK/T-cell lymphoma cells (Sun et al, 2015).…”

Section: Lymphomamentioning

confidence: 99%

BIRC5 (baculoviral IAP repeat containing 5)

Branco¹,

Jimenez²,

Machado-Neto³

et al. 2019

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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BIRC5, also known as survivin, has been implicated in cell cycle progression and apoptosis avoidance. BIRC5 is highly expressed in embryonic tissues, however very low or absent in adult tissues. BIRC5 overexpression has been frequently associated to cancer development, a poor prognosis and chemoresistance. Besides that, different BIRC5 isoforms has been characterized and related to better or worse chemotherapy responses depending on the isoform and the cancer type. So far, many efforts have been conducted in order to deplete BIRC5 in cancer cells, including gene therapy, pharmacological and nanotechnological approaches. In this review, we will discuss the role of BIRC5 in cancer cell biology and its clinical significance, demonstrating its DNA/RNA and protein aspects, also its relevance for diagnosis and prognosis, and advances as a target for the treatment of different cancer types.

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Sensitizing B- and T- cell Lymphoma Cells to Paclitaxel/Abraxane–Induced Death by AS101 via Inhibition of the VLA-4–IL10–Survivin Axis

Cited by 18 publications

References 46 publications

Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

The Small Tellurium Compound AS101 Ameliorates Rat Crescentic Glomerulonephritis: Association with Inhibition of Macrophage Caspase-1 Activity via Very Late Antigen-4 Inactivation

BIRC5 (baculoviral IAP repeat containing 5)

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