EurekaMag.com logo
+ Site Statistics
References:
48,253,228
Abstracts:
22,798,842
+ Resolve Accession
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
EurekaMag PDF Full Text Supply ServicePDF Full Text Supply Service
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
Submit PDF Full TextSubmit PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn
Follow on LinkedInFollow on Tumblr

+ Translate

Sulfasalazine inhibits growth of mantle cell lymphoma cell cultures via cyst ine starvation and delays tumour growth in a newly developed murine MCL model


, : Sulfasalazine inhibits growth of mantle cell lymphoma cell cultures via cyst ine starvation and delays tumour growth in a newly developed murine MCL model. Blood 102(11): 649a-650a, November 16

Introduction: Cyst(e)ine deficiency within lymphoid cells leads to a rapid decline in their levels of glutathione (a major free radical scavenger), loss of defense against oxidative stress, and subsequently apoptosis. Lymphoid cells cannot synthesize the amino acid and depend for growth and viability on its uptake from their micro-environment. Since lymphomas have been shown to retain the inability to synthesize cyst(e)ine they are potentially susceptible to cyst(e)ine starvation-based therapy. We have previously demonstrated that sulfasalazine (SASP), a drug used for treatment of severe inflammatory bowel disease and rheumatoid arthritis, is a potent inhibitor of the cystine/glutamate antiporter, xc-, a major plasma membrane cystine transporter. SASP abrogated growth of T and B lymphoma cell cultures via cystine starvation; SASP, administered intraperitoneally, markedly inhibited growth of rat Nb2-U17 lymphoma transplants in Nb rats without major toxicity to the hosts (Anti-Cancer Drugs 14:21, 2003). In the present study we investigated the usefulness of SASP in our newly developed model of MCL, a B-cell non-Hodgkin lymphoma (NHL), characterized by cyclin D1 and BCL2 over-expression. Results: Growth of human MCL cultures in Fischer's medium, supplemented with 10% fetal bovine serum and antibiotics, was markedly inhibited by SASP at therapeutic concentrations, showing IC50s of 0.13 and 0.30 for Z138C and Granta MCL cultures, respectively. Culture growth arrest could be largely prevented by enhancing cellular cystine uptake using 66 uM 2-mercaptoethanol (reported to promote cystine uptake via the leucine transporter), indicating that the SASP-induced inhibition resulted from cyst(e)ine starvation. A study into the efficacy of SASP in vivo was initiated using SCID/Rag2-M mice injected subcutaneously with Z138C cells (5 million cells/mouse); such a procedure leads to consistent development of tumours within 28 days. When tumours had reached a weight of about 0.1 gr, groups of six mice were treated for 10 consecutive days with saline (controls) or SASP (250 mg/kg body weight i.p., b.i.d.), a dosage well below the maximally tolerated dosage (300 mg/kg every 8 hr). It was found that treatment with SASP inhibited tumour growth, showing a delay in growth of at least 7 days, without major toxicity. Conclusions: SASP has a marked inhibitory effect on growth of MCL cell lines in vitro, an effect also seen in vivo in our murine SC MCL model. SASP may represent a novel approach for MCL treatment. The precise molecular consequences of SASP treatment on MCL cells warrant further investigation. Additional studies on the effect of SASP at higher dosages and in combination with cyclophosphamide and targeted therapies, eg. ASO and monoclonal antibodies against bcl-2, are in progress.

(PDF 0-2 workdays service)

Order PDF Full Text

Close
Close

Click here to order any other PDF Full Text


Accession: 035794983

PDF Full Text: Submit


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Other references

Coogan, P.F.; Rosenberg, L.; Strom, B.L., 2007: Statin use and the risk of 10 cancers. Statins affect the proliferation, survival, and migration of cancer cells, and it is thought that they may have chemopreventive properties in humans. The purpose of the present study was to evaluate the association between statin use and various t...

Tsukahara Y.; Takahashi T., 1973: Visual stimulator for electro encephalographic activation. Electroencephalography & Clinical Neurophysiology 35(3): 333-335

Ward, Dj, 1975: Report of field meeting to Abbey Wood, London. Tertiary Times3: 97-98

Tuller, Stanton E., 1997: Climatic controls of the cool human thermal sensation in a summertime onshore wind. Afternoon observations in summer comparing shoreline with inland atmospheric conditions were made during onshore winds at Victoria, British Columbia, Canada. The onshore wind came from a cool water surface. Mean monthly water temperatures near to...

Graflinger, Trude, 1930: Zur Kenntnis der Kleinarten von Uromyces scillarum. Schneider's discovery that the U. scillarum from Muscari racemosum is pathologically distinct, and incapable of passing over to other spp. of Muscari or to Hyacinthus or Scilla spp., led the author to make precise measurements of spore length...

Vanzetti, C., 1964: Land and man in Africa. An introductory account is given of the major orographie, climatic and vegetational features of the continent, and an examination made of the various historical processes and events affecting the population. In the light of these physical and huma...

Wyllie, I.; Dale, L.; Newton, I., 1996: Unequal sex-ratio, mortality causes and pollutant residues in long-eared owls in Britain. Recent reports have indicated an uneven sex-ratio among wintering Long-eared Owls Asio otus, in favour of males in Norway and females in Britain. Harvey and Riddiford (1990) found a ratio of 28 female female : 8 male male among trapped autumn migr...

PERNOD, J.; CHAMBATTE, C.; KERMAREC, J.; BATIME, J., 1963: Prognosis Of Endothoracic Sarcoidosis In The Young Adult. Bulletins et Memoires de la Societe Medicale des Hopitaux de Paris 114: 859-868

Hunnicutt, L.; Aadland, D., 2003: Inventory constraints in a dynamic model of imperfect competition: an application to beef packing. This paper incorporates inventory dynamics into a standard conjectural variations analysis of market power. Using a model which incorporates closed-loop equilibrium strategies, we show that measures of market power that ignore inventory dynamics a...

Wheeler, J., 1964: Waders of Cairns esplanade. North Queensland Naturalist, 32(135): 9-10