Compounds > n(1)-guanyl-1-7-diaminoheptane

n(1)-guanyl-1-7-diaminoheptane and Mouth-Neoplasms

n(1)-guanyl-1-7-diaminoheptane has been researched along with Mouth-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for n(1)-guanyl-1-7-diaminoheptane and Mouth-Neoplasms

Article	Year
GC7 enhances cisplatin sensitivity via STAT3 signaling pathway inhibition and eIF5A2 inactivation in mesenchymal phenotype oral cancer cells. Oncology reports, 2018, Volume: 39, Issue:3 Eukaryotic initiation factor 5A2 (eIF5A2), a newly identified oncogene, promotes cell survival, proliferation and motility in tumorigenesis. Drug resistance and dose-related adverse side-effects greatly reduce the efficiency and safety of cisplatin-based chemotherapy in advanced or recurrent oral squamous cell carcinoma (OSCC) patients. The present study investigated the effect of eIF5A2 combined with N1-guanyl-1,7-diaminoheptane (GC7, a novel eIF5A2 inhibitor) or siRNA. We found that low concentrations of GC7 (≤5 µM) had little effect on OSCC cell viability, but significantly enhanced cisplatin cytotoxicity. Compared with cisplatin, GC7/cisplatin had little effect on cisplatin-promoted mesenchymal-epithelial transition in mesenchymal phenotype Tca8113 and HN30 cells, or on cisplatin-induced epithelial-mesenchymal transition (EMT) in epithelial phenotype Cal27 and HN4 cells. Further research revealed that the upregulation of p-STAT3 and c-Myc which was induced by the single treatment with either cisplatin or GC7 was significantly reversed by the GC7/cisplatin combination in mesenchymal phenotype Tca8113 and HN30 cells. In in vivo treatment, we revealed that the GC7/cisplatin combination presented significant tumor volume reduction without distinct body weight loss. In conclusion, our data indicated that eIF5A2 is a potent therapeutic target in OSCC treatment. Our results revealed a novel mechanism by which GC7/cisplatin combination therapy may offer an efficient and safe therapeutic alternative to advanced or recurrent OSCC patients. Topics: Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Proliferation; Cisplatin; Drug Synergism; Epithelial-Mesenchymal Transition; Eukaryotic Translation Initiation Factor 5A; Guanine; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Peptide Initiation Factors; RNA-Binding Proteins; Signal Transduction; STAT3 Transcription Factor; Tumor Cells, Cultured; Xenograft Model Antitumor Assays	2018
N(1)-guanyl-1,7,-diamineoheptane, an inhibitor of deoxyhypusine synthase, suppresses differentiation and induces apoptosis via mitochondrial and AMPK pathways in immortalized and malignant human oral keratinocytes. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2009, Volume: 38, Issue:10 Although N(1)-guanyl-1,7,-diamineoheptane (GC7), an inhibitor of deoxyhypusine synthase, has been shown to inhibit cell growth, the mechanism of its action is not completely understood. In this study, we investigated the mechanisms of the effects of GC7 on cell growth, differentiation and apoptosis in relation to adenosine monophosphate-activated protein kinase (AMPK) activation, as AMPK is known to be a possible target for cancer treatment.. The effects of GC7 on the growth of immortalized human oral keratinocytes (IHOK) and primary oral cancer cells (HN4), was investigated using MTT assay, Western blotting, cell cycle analysis, DNA fragmentation and expression of apoptotic pathway proteins.. N(1)-guanyl-1,7,-diamineoheptane inhibited cell proliferation in a time- and dose-dependent manner in IHOK and HN4 cells. GC7 treatment decreased the expression of differentiation markers, such as involucrin, CK13 and CK19. The major mechanism of growth inhibition by GC7 treatment was induction of apoptosis, which is supported by sub-G(1) phase arrest, annexin V-FITC staining and DNA fragmentation analysis. GC7 treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation. GC7 treatment also resulted in a strong activation of AMPK. Furthermore, specific AMPK activator blocked the GC7-induced growth inhibition effect, as well as apoptosis.. These results demonstrate that GC7 blocks immortalized and malignant keratinocyte cell proliferation and differentiation by inducing apoptosis through the mitochondrial and AMPK pathways. On the basis of these observations, we propose that a strategy combining GC7 and AMPK inhibition could be developed into a novel chemotherapeutic modality in oral cancer. Topics: AMP-Activated Protein Kinases; Annexin A5; Apoptosis; Carcinoma; Caspase 3; Cell Cycle Proteins; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Proliferation; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; G1 Phase; Guanine; Humans; Keratin-13; Keratin-19; Keratinocytes; Mitochondria; Mouth Mucosa; Mouth Neoplasms; Oxidoreductases Acting on CH-NH Group Donors; Protein Precursors	2009

Article

Year

GC7 enhances cisplatin sensitivity via STAT3 signaling pathway inhibition and eIF5A2 inactivation in mesenchymal phenotype oral cancer cells.

Oncology reports, 2018, Volume: 39, Issue:3

Eukaryotic initiation factor 5A2 (eIF5A2), a newly identified oncogene, promotes cell survival, proliferation and motility in tumorigenesis. Drug resistance and dose-related adverse side-effects greatly reduce the efficiency and safety of cisplatin-based chemotherapy in advanced or recurrent oral squamous cell carcinoma (OSCC) patients. The present study investigated the effect of eIF5A2 combined with N1-guanyl-1,7-diaminoheptane (GC7, a novel eIF5A2 inhibitor) or siRNA. We found that low concentrations of GC7 (≤5 µM) had little effect on OSCC cell viability, but significantly enhanced cisplatin cytotoxicity. Compared with cisplatin, GC7/cisplatin had little effect on cisplatin-promoted mesenchymal-epithelial transition in mesenchymal phenotype Tca8113 and HN30 cells, or on cisplatin-induced epithelial-mesenchymal transition (EMT) in epithelial phenotype Cal27 and HN4 cells. Further research revealed that the upregulation of p-STAT3 and c-Myc which was induced by the single treatment with either cisplatin or GC7 was significantly reversed by the GC7/cisplatin combination in mesenchymal phenotype Tca8113 and HN30 cells. In in vivo treatment, we revealed that the GC7/cisplatin combination presented significant tumor volume reduction without distinct body weight loss. In conclusion, our data indicated that eIF5A2 is a potent therapeutic target in OSCC treatment. Our results revealed a novel mechanism by which GC7/cisplatin combination therapy may offer an efficient and safe therapeutic alternative to advanced or recurrent OSCC patients.

Topics: Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Proliferation; Cisplatin; Drug Synergism; Epithelial-Mesenchymal Transition; Eukaryotic Translation Initiation Factor 5A; Guanine; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Peptide Initiation Factors; RNA-Binding Proteins; Signal Transduction; STAT3 Transcription Factor; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

2018

N(1)-guanyl-1,7,-diamineoheptane, an inhibitor of deoxyhypusine synthase, suppresses differentiation and induces apoptosis via mitochondrial and AMPK pathways in immortalized and malignant human oral keratinocytes.

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2009, Volume: 38, Issue:10

Although N(1)-guanyl-1,7,-diamineoheptane (GC7), an inhibitor of deoxyhypusine synthase, has been shown to inhibit cell growth, the mechanism of its action is not completely understood. In this study, we investigated the mechanisms of the effects of GC7 on cell growth, differentiation and apoptosis in relation to adenosine monophosphate-activated protein kinase (AMPK) activation, as AMPK is known to be a possible target for cancer treatment.. The effects of GC7 on the growth of immortalized human oral keratinocytes (IHOK) and primary oral cancer cells (HN4), was investigated using MTT assay, Western blotting, cell cycle analysis, DNA fragmentation and expression of apoptotic pathway proteins.. N(1)-guanyl-1,7,-diamineoheptane inhibited cell proliferation in a time- and dose-dependent manner in IHOK and HN4 cells. GC7 treatment decreased the expression of differentiation markers, such as involucrin, CK13 and CK19. The major mechanism of growth inhibition by GC7 treatment was induction of apoptosis, which is supported by sub-G(1) phase arrest, annexin V-FITC staining and DNA fragmentation analysis. GC7 treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation. GC7 treatment also resulted in a strong activation of AMPK. Furthermore, specific AMPK activator blocked the GC7-induced growth inhibition effect, as well as apoptosis.. These results demonstrate that GC7 blocks immortalized and malignant keratinocyte cell proliferation and differentiation by inducing apoptosis through the mitochondrial and AMPK pathways. On the basis of these observations, we propose that a strategy combining GC7 and AMPK inhibition could be developed into a novel chemotherapeutic modality in oral cancer.

Topics: AMP-Activated Protein Kinases; Annexin A5; Apoptosis; Carcinoma; Caspase 3; Cell Cycle Proteins; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Proliferation; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; G1 Phase; Guanine; Humans; Keratin-13; Keratin-19; Keratinocytes; Mitochondria; Mouth Mucosa; Mouth Neoplasms; Oxidoreductases Acting on CH-NH Group Donors; Protein Precursors

2009