Guanylate Cyclase Activity in Human Leukemic and Normal
Lymphocytes

Dj, Takemoto; C, Dunford; Vaughn, Duke A.; Kj, Kramer; Smith, Allen; Rg, Powell

doi:10.1159/000459047

Cited by 28 publications

(11 citation statements)

References 11 publications

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“…cAMP and cGMP were thought to act as biological antagonists in the regulation of cell growth at the beginning (Goldberg et al, 1975), and elevated cGMP levels have been observed in certain human tumor tissues (Hadden et al, 1972;DeRubertis et al, 1976;Takemoto et al, 1982). Increased urinary cGMP in rats with hepatoma or renal tumor implants was also detected by Murad et al (1975) and Criss and Murad (1976).…”

Section: Discussionmentioning

confidence: 99%

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Zhu¹,

Li²,

Zheng³

et al. 2011

Mol Pharmacol

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The NO and cGMP signaling pathways are of broad physiological and pathological significance. We compared the NO/soluble guanylyl cyclase (sGC)/cGMP pathway in human glioma tissues and cell lines with that of healthy control samples and demonstrated that sGC expression is significantly lower in glioma preparations. Our analysis of GEO databases (National Cancer Institute) further revealed a statistically significant reduction of sGC transcript levels in human glioma specimens. On the other hand, the expression levels of particulate (membrane) guanylyl cyclases (pGC) and cGMP-specific phosphodiesterase (PDE) were intact in the glioma cells that we have tested. Pharmacologically manipulating endogenous cGMP generation in glioma cells through either stimulating pGC by ANP/BNP, or blocking PDE by 3-isobutyl-1-methylxanthine/ zaprinast caused significant inhibition of proliferation and colony formation of glioma cells. Genetically restoring sGC expression also correlated inversely with glioma cells growth. Orthotopic implantation of glioma cells transfected with an active mutant form of sGC (sGC␣1␤1 Cys105 ) in athymic mice increased the survival time by 4-fold over the control. Histological analysis of xenografts overexpressing ␣1␤1Cys105 sGC revealed changes in cellular architecture that resemble the morphology of normal cells. In addition, a decrease in angiogenesis contributed to glioma inhibition by sGC/cGMP therapy. Our study proposes the new concept that suppressed expression of sGC, a key enzyme in the NO/cGMP pathway, may be associated with an aggressive course of glioma. The sGC/ cGMP signaling-targeted therapy may be a favorable alternative to chemotherapy and radiotherapy for glioma and perhaps other tumors.

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Section: Discussionmentioning

confidence: 99%

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Zhu¹,

Li²,

Zheng³

et al. 2011

Mol Pharmacol

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“…Alpha-and beta-momorcharin, momordin, and cucurbitacin B from MC have clinically demonstrated ability to inhibit guanylate cyclase linked to pathogenesis and replication of leukemia and other cancers (Takemoto et al, 1982b).…”

Section: Experimental Studiesmentioning

confidence: 99%

“…MC has demonstrated the ability to inhibit an enzyme named guanylate cyclase in a clinical setting (Takemoto et al, 1982b). A conjugate of momordin, monoclonal antibody (named 8A) and plasma antigen was tried for ex vivo purging in autologous bone marrow transplantation in multiple myeloma patients.…”

Section: Clinicalmentioning

confidence: 99%

Pharmacological actions and potential uses of Momordica charantia: a review

Grover

Yadav

2004

Journal of Ethnopharmacology

678

380

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“…Whole fruit aqueous extracts of a Chinese bitter melon have displayed preferential cytotoxicity towards breast cancer and leukemia cells, without effecting the viability of normal cells. 29, 30 Similarly, saponin-rich extracts selectively induced apoptosis in hepatoma cells, without causing the same effect in their normal counterparts. 31 In this study, the SE did not discriminate in its cytotoxic activity and, in fact, was more potent to the HPDE cells.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effect of Bitter Melon (Momordica charantia L.) Ethanol Extract and Its Fractions on Pancreatic Cancer Cells in vitro

Richmond¹,

Vuong²,

Scarlett³

2017

Exploratory Research and Hypothesis in Medicine

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IntroductionPancreatic cancer (PC) is the fourth most lethal form of cancer in Western society, with mortality closely mirroring incidence and an overall 5-year survival of less than 7%. 1,2 Upon diagnosis, only 20% of patients are eligible for surgery, the only potential cure to date, with the remainder in advanced stages of the disease.Surgery is invasive due to the physical location of the pancreas and is often used as a treatment option in combination with chemotherapy. Despite this, a majority of patients who undergo surgery suffer a relapse from metastatic disease or experience comorbidities such as venothromboembolic disease. 3-5 Chemotherapy for PC patients involves treatment with agents such as the standard chemotherapeutic anti-metabolite drug gemcitabine (a pyrimidine analogue), or adjuvant therapy with additional agents such as the anti-tubulin agent nab-paclitaxel that can block nuclear division, causing cell death. 3,6,7 Combination drug 5-fluorouracil/folinic acid, irinotecan and oxaliplatin (FOLFIRINOX) is also a common treatment option but despite better response and survival rates than with single-agent gemcitabine treatment, FOLFIRINOX has greater levels of toxicity. 3 Chemotherapy outcomes are varied due to physical and genetic obstacles of PC that cause complications, as they can Keywords: Bitter melon; Pancreatic cancer; Herbal medicine. Abbreviations: AE, aescin equivalent; BMJ, bitter melon juice; CCK-8, Cell Counting Kit-8; CE, crude ethanol extract; CuB, Cucurbitacin B; F1, fraction 1; F2, fraction 2; F3, fraction 3; FBS, fetal bovine serum; GI50, minimum 50% growth inhibitory concentration; HPDE, human pancreatic ductal epithelial; HPLC, high-pressure liquid chromatography; L-Glu, L-glutamine; PBS, phosphate-buffered saline; PC, pancreatic cancer; SE, saponin-enriched extract. Cytotoxic Effect of Bitter Melon (Momordica charantia L.) Ethanol Extract and Its Fractions on Pancreatic Cancer Cells in vitro AbstractBackground and objectives: The incidence of pancreatic cancer (PC) closely matches mortality, with current therapies ineffective often due to late diagnosis and difficulties in drug delivery. Bitter melon (Momordica charantia, Cucurbitaceae) has been traditionally used as an herbal medicine, particularly for the treatment of diabetes, in South East Asian countries. The aim of this study was to investigate the anti-PC potential of a crude ethanol extract (CE) and its enriched fractions.

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Guanylate Cyclase Activity in Human Leukemic and Normal Lymphocytes

Cited by 28 publications

References 11 publications

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Pharmacological actions and potential uses of Momordica charantia: a review

Cytotoxic Effect of Bitter Melon (Momordica charantia L.) Ethanol Extract and Its Fractions on Pancreatic Cancer Cells in vitro

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