N-Terminal Domain of Fragile Histidine Triad Exerts Potent Cytotoxic Effect in HT1080 Cells and Increases Doxorubicin Cytotoxicity

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ESLAMPARAST AMENEH; Abbasgholizadeh Reza; OSTAD SEYED NASSER; Gharghabi Mehdi; GHAHREMANI MOHAMMAD HOSSEIN

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Journal Paper

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Journal: Iranian Journal of Pharmaceutical Research Year:2019 | Volume:18 | Issue:1 Page(s): 254-262

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Title

N-Terminal Domain of Fragile Histidine Triad Exerts Potent Cytotoxic Effect in HT1080 Cells and Increases Doxorubicin Cytotoxicity

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Keywords

Fragile histidine triad

HT1080

Doxorubicin

Combination therapy

MTT assay

Flowcytometry

Abstract

Fragile histidine triad (FHIT) serves a critical function as a tumor suppressor that inhibits p53 degradation by mouse double minute 2 (MDM2). The functional domains of FHIT involved in tumor inhibition was interpreted. In-silico screening data were employed to construct truncated forms of FHIT to assess their cytotoxic effects on the HT1080 cell line. Full FHIT expression was confirmed by western blotting and expression of two FHIT truncates were confirmed by RT-PCR. Transfection of these truncated forms into HT1080 cells showed that the N-terminal truncated form (amino acids 17-102) better inhibited proliferation than the full-length FHIT. The combined effects of these truncated forms augmented Doxorubicin-induced cytotoxicity. Functional analysis demonstrated that these fragments and their combination with Doxorubicin can arrest cells in the G2 phase of the cell cycle as specified by flow cytometry. The FHIT functional domains can be used as lead compounds for development of drug designs and gene transfer for cancer therapy.

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APA: Copy

ESLAMPARAST, AMENEH, Abbasgholizadeh, Reza, OSTAD, SEYED NASSER, Gharghabi, Mehdi, & GHAHREMANI, MOHAMMAD HOSSEIN. (2019). N-Terminal Domain of Fragile Histidine Triad Exerts Potent Cytotoxic Effect in HT1080 Cells and Increases Doxorubicin Cytotoxicity. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 18(1), 254-262. SID. https://sid.ir/paper/289212/en

Vancouver: Copy

ESLAMPARAST AMENEH, Abbasgholizadeh Reza, OSTAD SEYED NASSER, Gharghabi Mehdi, GHAHREMANI MOHAMMAD HOSSEIN. N-Terminal Domain of Fragile Histidine Triad Exerts Potent Cytotoxic Effect in HT1080 Cells and Increases Doxorubicin Cytotoxicity. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2019;18(1):254-262. Available from: https://sid.ir/paper/289212/en

IEEE: Copy

AMENEH ESLAMPARAST, Reza Abbasgholizadeh, SEYED NASSER OSTAD, Mehdi Gharghabi, and MOHAMMAD HOSSEIN GHAHREMANI, “N-Terminal Domain of Fragile Histidine Triad Exerts Potent Cytotoxic Effect in HT1080 Cells and Increases Doxorubicin Cytotoxicity,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 18, no. 1, pp. 254–262, 2019, [Online]. Available: https://sid.ir/paper/289212/en

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