scholarly journals The Fhit protein: an opportunity to overcome chemoresistance

Aging ◽  
2016 ◽  
Vol 8 (11) ◽  
pp. 3147-3150 ◽  
Author(s):  
Eugenio Gaudio ◽  
Francesco Paduano ◽  
Carlo M. Croce ◽  
Francesco Trapasso
Keyword(s):  
Fhit Protein

scholarly journals Tanshinones induce tumor cell apoptosis via directly targeting FHIT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianglian Zhou ◽  
Yuting Pan ◽  
Yue Wang ◽  
Bojun Wang ◽  
Yu Yan ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Tanshinone Iia ◽  
Binding Affinities ◽  
Tumor Cell Apoptosis ◽  
Anti Cancer ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Direct Binding ◽  
Fhit Protein ◽  
Diadenosine Triphosphate

AbstractThe liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.

scholarly journals Human diadenosine triphosphate hydrolase: preliminary characterisation and comparison with the Fhit protein, a human tumour suppressor.

2000 ◽  
Vol 47 (2) ◽  
pp. 435-441 ◽  
Author(s):  
A C Asensio ◽  
C R Rodríguez-Ferrer ◽  
S Oaknin ◽  
P Rotllán
Keyword(s):  
Protein A ◽  
Gel Filtration ◽  
Human Platelets ◽  
Tumour Suppressor ◽  
Human Tumour ◽  
Fhit Protein ◽  
Diadenosine Triphosphate

Human platelets diadenosine triphosphatase was characterised and compared with the Fhit protein, a human tumour suppressor with diadenosine triphosphatase activity. Both enzymes exhibit similar Km, are similarly activated by Mg2+, Ca2+ and Mn2+, and inhibited by Zn2+ and suramin. However, they are differentially inhibited by Fhit antibodies and exhibit differences in gel-filtration behaviour.

scholarly journals Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions

2003 ◽  
pp. 81-87 ◽  
Author(s):  
GE Thomopoulou ◽  
S Tseleni-Balafouta ◽  
AC Lazaris ◽  
H Koutselini ◽  
N Kavantzas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Control ◽  
Parathyroid Glands ◽  
Considerable Proportion ◽  
Parathyroid Cell ◽  
Apoptotic Cells ◽  
Cell Cycle Regulators ◽  
Suppressor Activity ◽  
Fhit Protein

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

FHIT protein enhances paclitaxel-induced apoptosis in lung cancer cells

2006 ◽  
Vol 118 (7) ◽  
pp. 1692-1698 ◽  
Author(s):  
Cheol Hyeon Kim ◽  
Jung Sun Yoo ◽  
Choon-Taek Lee ◽  
Young Whan Kim ◽  
Sung Koo Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Fhit Protein ◽  
Induced Apoptosis

Fhit protein expression in human gastric cancer and related precancerous lesions

2001 ◽  
Author(s):  
Michele Caselli ◽  
Marco Marchisio ◽  
Michele Gaudio ◽  
Luca Saragoni ◽  
Giovanni Lanza ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Precancerous Lesions ◽  
Human Gastric Cancer ◽  
Fhit Protein

Immunohistochemical evaluation of Fhit protein expression in oral squamous cell carcinomas

2007 ◽  
Vol 28 (10) ◽  
pp. 433-437 ◽  
Author(s):  
W. F. P. Heerden ◽  
T. J. P. Swart ◽  
M. B. Heerden ◽  
E. J. Rensburg ◽  
S. Engelbrecht ◽  
...  
Keyword(s):  
Protein Expression ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Oral Squamous Cell Carcinomas ◽  
Fhit Protein

scholarly journals Loss of FHIT protein expression is related to high proliferation, low apoptosis and worse prognosis in non-small-cell lung cancer

2004 ◽  
Vol 17 (4) ◽  
pp. 440-448 ◽  
Author(s):  
Gemma Toledo ◽  
Jesús Javier Sola ◽  
Maria Dolores Lozano ◽  
Elena Soria ◽  
Javier Pardo
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Fhit Protein ◽  
Worse Prognosis
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