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Gamal-Eldeen Amira M.,Baghdadi Houry M.,Afifi Nermeen S.,Ismail Ebtehal M.,Alsanie Walaa F.,Althobaiti Fayez,Raafat Bassem M. 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.2
Background Oral tongue squamous cell carcinoma (OTSCC) is a popular aggressive malignancy of the oral cavity. Despite advances in OTSCC therapy, the overall 5-year survival rate is low. The tumor microenvironment resistance factors lead to chemotherapy failure, especially intratumoral hypoxia. HIF-1α, the main protein in hypoxia pathway, influences cell survival and angiogenesis. Hypoxia/HIF-1α system is a potential strategic target in cancer therapeutics. The expression of hypoxia-regulating miRNAs (hypoxamiRs; miR-210 and miR-21), regulators of HIF-1α, is high in OTSCC. Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs) have been reported as promising modality in cancer treatment. Objective This study aimed to investigate the influence of GA-AuNPs on the hypoxia regulators in OTSCC (CAL-127 cells). GA-AuNPs cytotoxicity assessed by MTT assay; cell death mode was detected by dual DNA staining; monitoring of cellular hypoxia was followed by pimonidazole; miR-210 and miR-21 expression was assessed by qPCR; and their targets (HIF-1α and c-Myc) assayed by immunocytofluorescence and ELISA, respectively. Results GA-AuNPs (75–80 nm; λmax of ~ 540 nm) reduced cell viability with IC50 of 392.3 and 247.3 µg/ml after 24 h and 48 h, respectively. Cell death was mainly due to apoptosis. CAL-27 cells exhibited high hypoxia and the treatment with GA-AuNPs inhibited this hypoxia in a dose-dependent manner, as detected by pimonidazole. GA-AuNPs (30% IC50) significantly reduced miR-210 and miR-21 expression. HIF-1α and c-Myc were inhibited by GA-AuNPs (30% IC50, for 48 h). Conclusion The study findings may suggest GA-AuNPs as a promising carrier for chemotherapies to diminish intratumoral hypoxia-stimulated resistance. Background Oral tongue squamous cell carcinoma (OTSCC) is a popular aggressive malignancy of the oral cavity. Despite advances in OTSCC therapy, the overall 5-year survival rate is low. The tumor microenvironment resistance factors lead to chemotherapy failure, especially intratumoral hypoxia. HIF-1α, the main protein in hypoxia pathway, influences cell survival and angiogenesis. Hypoxia/HIF-1α system is a potential strategic target in cancer therapeutics. The expression of hypoxia-regulating miRNAs (hypoxamiRs; miR-210 and miR-21), regulators of HIF-1α, is high in OTSCC. Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs) have been reported as promising modality in cancer treatment. Objective This study aimed to investigate the influence of GA-AuNPs on the hypoxia regulators in OTSCC (CAL-127 cells). GA-AuNPs cytotoxicity assessed by MTT assay; cell death mode was detected by dual DNA staining; monitoring of cellular hypoxia was followed by pimonidazole; miR-210 and miR-21 expression was assessed by qPCR; and their targets (HIF-1α and c-Myc) assayed by immunocytofluorescence and ELISA, respectively. Results GA-AuNPs (75–80 nm; λmax of ~ 540 nm) reduced cell viability with IC50 of 392.3 and 247.3 µg/ml after 24 h and 48 h, respectively. Cell death was mainly due to apoptosis. CAL-27 cells exhibited high hypoxia and the treatment with GA-AuNPs inhibited this hypoxia in a dose-dependent manner, as detected by pimonidazole. GA-AuNPs (30% IC50) significantly reduced miR-210 and miR-21 expression. HIF-1α and c-Myc were inhibited by GA-AuNPs (30% IC50, for 48 h). Conclusion The study findings may suggest GA-AuNPs as a promising carrier for chemotherapies to diminish intratumoral hypoxia-stimulated resistance.
A New Pyrrole Alkaloid Isolated from Arum palaestinum Boiss. and its Biological Activities
El-Desouky, S.K.,Kim, Ki-Hun,Ryu, Shi-Young,Eweas, Ahmad Farouk,Gamal-Eldeen, Amira M.,Kim, Young-Kyoon 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8
The phytochemical analysis of the ethyl acetate fraction of Arum palaestinum Boiss. (Araceae) led to the isolation and identification of a new polyhydroxy alkaloid compound; (S)-3,4,5-trihydroxy-1H-pyrrol-2(5H)-one (1), and other five known compounds; caffeic acid (2), isoorientin (3), luteolin (4) and vicenin II (5), as well as the rare compound 3,6,8-trimethoxy, 5,7,3',4'-tetrahydroxy flavone (6). The structural elucidations of all the compounds were based on spectroscopic data ($^1H-$ and $^{13}C-NMR$, DEPT, HSQC, HMBC and NOE difference techniques) and comparison with literature data. Investigation of the antioxidant activity of the ethyl acetate fraction indicated its strong scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals ($SC_{50}$ $3.1{\pm}0.82$ ${\mu}g/mL$). Moreover, the treatment of different human cancer cell lines with the ethyl acetate fraction led to dose-dependant suppression in the proliferation of both breast carcinoma cells (MCF-7; $IC_{50}$ $59.09{\pm}4.1$ ${\mu}g/mL$) and lymphoblastic leukemia cells (1301; $IC_{50}$ $53.1{\pm}2.9$ ${\mu}g/mL$); however, it was found to have no effect on the growth of hepatocellular carcinoma cells (Hep G2).
A New Pyrrole Alkaloid Isolated from Arum palaestinum Boiss. and its Biological Activities
S. K. El-Desouky,Ki Hun Kim,Shi Young Ryu,Ahmad Farouk Eweas,Amira M. Gamal-Eldeen,Young-Kyoon Kim 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8
The phytochemical analysis of the ethyl acetate fraction of Arum palaestinum Boiss. (Araceae) led to the isolation and identification of a new polyhydroxy alkaloid compound; (S)-3,4,5-trihydroxy- 1H-pyrrol-2(5H)-one (1), and other five known compounds; caffeic acid (2), isoorientin (3), luteolin (4) and vicenin II (5), as well as the rare compound 3,6,8-trimethoxy, 5,7,3',4'-tetrahydroxy flavone (6). The structural elucidations of all the compounds were based on spectroscopic data (1H- and 13C-NMR, DEPT, HSQC, HMBC and NOE difference techniques) and comparison with literature data. Investigation of the antioxidant activity of the ethyl acetate fraction indicated its strong scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals (SC50 3.1±0.82 μg/mL). Moreover, the treatment of different human cancer cell lines with the ethyl acetate fraction led to dose-dependant suppression in the proliferation of both breast carcinoma cells (MCF-7; IC50 59.09±4.1 μg/mL) and lymphoblastic leukemia cells (1301; IC50 53.1±2.9 μg/mL); however, it was found to have no effect on the growth of hepatocellular carcinoma cells (Hep G2).