Depletion of nucleophosmin via transglutaminase 2 cross-linking increases drug resistance in cancer cells

Park, Kang Seo; Han, Byeong Gu; Lee, Kyoung Hwa; Kim, Dae Seok; Kim, Jung Mo; Jeon, Hyesung; Kim, Hyoun Sook; Suh, Se Won; Lee, Eunjoo H.; Kim, Soo Youl; Lee, Byung Il

doi:10.1016/j.canlet.2008.09.007

Cited by 25 publications

(21 citation statements)

References 34 publications

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“…Nucleophosmin is a nucleolar multifunctional chaperone protein that plays a role in various cellular processes, including apoptosis, by shuttling between the nucleus and the cytoplasm [24]. Although nucleophosmin has an antiapoptotic function via Bax binding, depletion of cytosolic nucleophosmin can decrease the stability of the proapoptotic Bax protein and lead to antiapoptosis [25]. As just described, the down-regulation of 4 proapoptotic proteins in 5-FU-resistant cells could indicate that these cells have the ability to avoid apoptosis after 5-FU exposure, resulting in drug resistance in cancer cells.…”

Section: Down-regulation Of 4 Proapoptotic Proteinsmentioning

confidence: 99%

Identification of phosphorylated serine-15 and -82 residues of HSPB1 in 5-fluorouracil-resistant colorectal cancer cells by proteomics

Sakai¹,

Otani

Miyamoto

et al. 2012

Journal of Proteomics

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Section: Down-regulation Of 4 Proapoptotic Proteinsmentioning

confidence: 99%

Identification of phosphorylated serine-15 and -82 residues of HSPB1 in 5-fluorouracil-resistant colorectal cancer cells by proteomics

Sakai¹,

Otani

Miyamoto

et al. 2012

Journal of Proteomics

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“…tg-2 is overexpressed in many cancers such as breast cancer (4), malignant melanoma (5), and glioblastoma (6). the protein cross-linking activity by tg-2 is related to the resistance of chemotherapy agents (7). It is part of tumor biology because it is involved in the polymerization of the inhibitor of nF-κB (I-κB) (7).…”

Section: Introductionmentioning

confidence: 99%

“…the protein cross-linking activity by tg-2 is related to the resistance of chemotherapy agents (7). It is part of tumor biology because it is involved in the polymerization of the inhibitor of nF-κB (I-κB) (7). the polymerization of I-κB can produce many free forms of nF-κB.…”

Section: Introductionmentioning

confidence: 99%

4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells

Kim

Jeong²,

Park³

et al. 2011

Oncol Rep

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Abstract. resistance to chemotherapy is very important in the prognosis of tumors. transglutaminase-2 (tg-2) mediated chemotherapy resistance has been widely reported. the objective of this study was to demonstrate the effect of 4-hexylresorcinol (4-Hr) on tg-2 activity in nasopharyngeal squamous cell carcinoma cells (KB cells). treatment with a mixture of 4-HR and cisplatin significantly decreased KB cell viability compared to treatment by cisplatin alone at 10 µg/ml (p<0.001). 4-Hr inhibited tg-2 activity compared to cisplatin alone at 5, 10 and 20 µg/ml (p=0.001, 0.001 and 0.003, respectively). nuclear translocation of tg-2 was also inhibited by 4-Hr treatment. 4-Hr treatment also increased the fluorescence life-time of DAPI significantly compared to the untreated control or the cisplatin treated group (p<0.001).In conclusion, 4-HR inhibited TG-2 activity and showed a synergistic effect on tumor cell growth inhibition with cisplatin.

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“…TGase 2 is aberrantly activated in tissues and cells and contributes to neurodegenerative diseases, such as Alzheimer's disease (Citron et al, 2001), Parkinson's disease (Junn et al, 2003;Andrings et al, 2004), neuro-AIDS (Roberts et al, 2003), Huntington's diseases (Kim et al, 2005), hippocampal CA 1 ischemia (Hwang et al, 2009), celiac disease (Naiyer et al, 2008), lupus (Sanchez et al, 2000), autoimmune diseases like rheumatic arthritis (Picarelli et al, 2003), human atherosclerotic coronary arteries (Cho et al, 2008), breast cancers (Park et al, 2009a) and drug resistance in variety of cancer cells Park et al, 2009bPark et al, , 2010. TGase 2 expression is increased in inflammatory diseases such as activation of microglia, a hallmark of brain inflammation (Park et al, 2004), idiopathic inflammatory myopathies (Kim, 2006) and allergic asthma (Hallstrand et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

Kim

Park

Hong

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSETransglutaminase 2 (TGase 2) expression is increased in inflammatory diseases, and TGase 2 inhibitors block these increases. We examined whether the R2 peptide inhibited the expression of TGase 2 in a mouse model of inflammatory allergic asthma. EXPERIMENTAL APPROACHC57BL/6 mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. OVA-specific serum IgE and leukotrienes (LTs) levels were measured by enzyme-linked immunosorbent assay. Recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues and goblet cell hyperplasia were assessed histologically. Airway hyperresponsiveness was determined in a barometric plethysmographic chamber. Expression of TGase 2, eosinophil major basic protein (EMBP), the adhesion molecule vascular cell adhesion molecule-1, Muc5ac and phospholipase A2 (PLA2) protein were determined by Western blot. Expression of mRNAs of Muc5ac, cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were measured by reverse transcriptase-polymerase chain reaction and nuclear factor-kB (NF-kB) by electrophoretic mobility shift assay. KEY RESULTSR2 peptide reduced OVA-specific IgE levels; the number of total inflammatory cells, macrophages, neutrophils, lymphocytes and eosinophils in BAL fluid and the number of goblet cells. Airway hyperresponsiveness, TGase 2 and EMBP levels, mRNA levels of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, RANTES, tumour necrosis factor-a, and MMP2/9, Muc5ac, NF-kB activity, PLA2 activity and expressions, and LT levels in BAL cells and lung tissues were all reduced by R2 peptide. R2 peptide also restored expression of TIMP1/2. CONCLUSION AND IMPLICATIONSR2 peptide reduced allergic responses by regulating NF-kB/TGase 2 activity in a mouse model of allergic asthma. This peptide may be useful in the treatment of allergic asthma. AbbreviationsBAL, bronchoalveolar lavage; ELISA, enzyme-linked immunosorbent assay; EMBP, eosinophil major basic protein; EMSA, electrophoretic mobility shift assay; MMP, matrix metalloproteinase; NF-kB, nuclear factor-kappa B; OVA, ovalbumin; PAS, periodic acid-Schiff; PBS, phosphate buffered saline; PLA2, phospholipase A2; RT-PCR, reverse transcriptase-polymerase chain reaction; TGase 2, transglutaminase 2; TIMP, tissue inhibitor of matrix metalloproteinase BJP British Journal of Pharmacology

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Depletion of nucleophosmin via transglutaminase 2 cross-linking increases drug resistance in cancer cells

Cited by 25 publications

References 34 publications

Identification of phosphorylated serine-15 and -82 residues of HSPB1 in 5-fluorouracil-resistant colorectal cancer cells by proteomics

Identification of phosphorylated serine-15 and -82 residues of HSPB1 in 5-fluorouracil-resistant colorectal cancer cells by proteomics

4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells

Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

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