Effect of rMnSOD on Survival Signaling in Pediatric High Risk T‐Cell Acute Lymphoblastic Leukaemia

Pica, Alessandra; Santi, Annalisa Di; D’Angelo, Velia; Iannotta, Adriana; Ramaglia, M; Martino, Martina Di; Pollio, Maria Laura; Schiattarella, Antonella; Borrelli, Antonella; Mancini, Aldo; Indolfi, Paolo; Casale, Fiorina

doi:10.1002/jcp.24840

Cited by 8 publications

(8 citation statements)

References 19 publications

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“…Sonuç olarak, kemik iliği ve ekstramedüller bölgelerde fizyolojik hematopoez baskılanır ve lösemik hücreler birikir (10). Çocukluk çağında gelişen ALL, kemoterapiye karşı oldukça duyarlı olmasına rağmen, çocukların yaklaşık %25'inde nüks gözlenir (11). Yetişkinlerin ise daha büyük bir bölümünde tedaviden sonra nüks gözlenir ve hematopoietik kök hücre transplantasyonu dahil ileri tedavi yöntemle-ri genel sağkalımı sınırlı bir oranda artırmaktadır.…”

Section: Tartişma Ve Sonuçunclassified

Telomerase Inhibitor BIBR1532 Increases the Expression of CDH13, DAPK1, NR4A3 Genes in Acute Lymphoblastic Leukemia Cells and Induced Apoptosis

Özateş¹,

Goker²,

Doğan³

et al. 2017

LLM Dergi

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Akut lenfoblastik lösemi (ALL), kemik iliği veya diğer lenfoid dokulardaki lenfoid progenitör hücrelerin farklılaşma ve çoğalma anomalilerinden kaynaklanan hematolojik malignitedir. Telomeraz inhibitörleri çoğalmayı ve büyümeyi önleyen bir diğer önemli antikanser ajanlardır. BIBR1532, keşfedildiği günden beri, oldukça etkili bir hTERT inhibitörü olarak kullanılmaktadır. Bu çalışmada, BIBR1532'nin yetişkin akut lenfoblastik lösemi hücre hattı olan CCRF-CEM üzerindeki sitotoksik etkisinin kontrol grubuyla kıyaslanarak belirlenmesi amaçlanmıştır. Hastalar ve Yöntem: BIBR1532'nin CCRF-CEM hücre hattı üzerindeki etkisi WST-1 analizi ile belirlenmiştir. Apoptozun belirlenmesinde Annexin V yöntemi kullanılmıştır. Gen ekspresyon değişiklikleri gerçek zamanlı polimeraz zincir reaksiyonu (PCR) ile belirlenmiştir. Bulgular: BIBR1532'nin CCRF-CEM hücre hattı üzerindeki IC 50 dozu 48 saat sonunda 89 μM olarak belirlenmiştir. Aynı zamanda apoptozu kontrole göre %7 artırdığı ve CDH13, DAPK1 ve NR4A3 genlerinin ekspresyon seviyelerinde belirgin bir artışa sebep olduğu belirlenmiştir. Sonuç: Sonuç olarak elde ettiğimiz bulgulara göre ALL tedavisinde telomeraz inhibitörü BIBR1532 kullanımı, telomeraz aktivitesini düşürebileceği gibi apoptotik hücre ölümünü de uyarabilir. Ayrıca bu yolakta görevli genlerin anlamlı ekspresyon değişikliğinin olması hastalığın moleküler patolojisinin aydınlatılmasına ve alternatif tedavi hedefi olabilecek genlerin belirlenmesine katkı sağlayabilir.

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Section: Tartişma Ve Sonuçunclassified

Telomerase Inhibitor BIBR1532 Increases the Expression of CDH13, DAPK1, NR4A3 Genes in Acute Lymphoblastic Leukemia Cells and Induced Apoptosis

Özateş¹,

Goker²,

Doğan³

et al. 2017

LLM Dergi

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“…rMnSOD appears to be very effective at O2 scavenging both intra and extracellularly and at improving pathological conditions associated with increased oxidative stress . rMnSOD in leukemic T cells, but not in Jurkat cells, induced apoptosis by inhibiting the phosphorylation of ERK kinase . In mammary tumors increases the effectiveness cisplatin .…”

Section: Introductionmentioning

confidence: 99%

Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562 cells

Damiano

Montagnaro²,

Puzio³

et al. 2018

J of Cellular Biochemistry

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In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study, we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation, and apoptosis. To test the possible mechanisms of action of such antioxidants, we utilized N-acetyl-L-cysteine (NAC) a specific inhibitor ROS production or PP1 a specific Src tyrosine kinase inhibitor or BAPTA a specific chelator of intracellular calcium. Our data demonstrated: 1) RES, rMnSOD, δ-TOCO, and NAC, at dose used, significantly reduced the intracellular levels of MDA induced by DAS or NIL; 2) RES, rMnSOD, and δ-TOCO increased the intracellular ROS levels; 3) The increase ROS levels is related to higher levels of oligonucleosomesi induced by DAS and NIL and that NAC significantly reduced this activity. Interestingly, our data showed that apoptotic activity of DAS and NIL have significantly increased the production of oligonucleosomes by triggering excessive ROS generation as well as functionality of SERCA receptors.

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“…Thus, rMnSOD has the invaluable advantage, over the native enzyme, of being able to easily enter into the cells and tissues thanks to the persistence in the recombinant mature protein of its leader peptide. Consequently, treatment side effects should be significantly reduced in comparison with traditional treatments [17,18].…”

Section: Introductionmentioning

confidence: 99%

Neutral Sphingomyelinase Modulation in the Protective/Preventive Role of rMnSOD from Radiation-Induced Damage in the Brain

Cataldi

Borrelli

Ceccarini

et al. 2019

IJMS

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Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme.

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Effect of rMnSOD on Survival Signaling in Pediatric High Risk T‐Cell Acute Lymphoblastic Leukaemia

Cited by 8 publications

References 19 publications

Telomerase Inhibitor BIBR1532 Increases the Expression of CDH13, DAPK1, NR4A3 Genes in Acute Lymphoblastic Leukemia Cells and Induced Apoptosis

Telomerase Inhibitor BIBR1532 Increases the Expression of CDH13, DAPK1, NR4A3 Genes in Acute Lymphoblastic Leukemia Cells and Induced Apoptosis

Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562 cells

Neutral Sphingomyelinase Modulation in the Protective/Preventive Role of rMnSOD from Radiation-Induced Damage in the Brain

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