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        Anti-cancer Effect of Hyoscyamus muticus Extract via Its Activation of Fas/FasL-ASK1-p38 Pathway

        Amer Ali Abd El-Hafeez,Hala Mohamed M. Marzouk,Mohamed A. A. Abdelhamid,Hazim O. Khalifa,Tamer H. A. Hasanin,Ahmed G. K. Habib,Fatma Mahmoud Abdelwahed,Fatma M. Barakat,Eslam M. Bastawy,Eman M. B. Abd 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.5

        Hyoscyamus muticus L. is a traditional medicine used as antispasmodic and sedative. Herein, we aimed to determine the phytochemical constituents and for the first time its anti-cancer activities. The phytochemical constituents of the different extracts were evaluated by calorimetric methods. The anti-cancer activities of the extracts were tested against leukemia, breast, renal, and prostate cancers cell lines. 4, 6-Diamidino-2-phenylindole (DAPI) staining, flow cytometric analysis, knockdown of ASK1, and reactive oxygen species (ROS) production were evaluated to clarify the mechanism of action. Phytochemical screening confirmed the presence of wide range of phytoconstituents. Hyoscyamus muticus methanolic extracts (HMME) showed the highest anti-cancer activities against leukemia, breast, renal, and prostate cancers as compared to ethanol and aqueous extracts. Specifically, HMME exerted cytotoxic effect against the MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cell lines with IC50 values of 8.75 and 7.25 μg/mL, respectively. Mechanistically, DAPI staining and flow cytometric analysis revealed that HMME induces apoptosis via the death receptor, FAS, but not the mitochondrial pathway. Moreover, ASK1 and p38 were rapidly activated in response to HMME, and knockdown of ASK1 by a small interference of RNA specific to Ask1 attenuated p38 and caspase-3 activation and suppressed apoptosis, implying that HMME-induced apoptosis relies on the ASK1-p38-caspase-3 pathway. Furthermore, we confirmed that cellular ROS generation was a critical mediator in HMME-induced apoptosis because the ROSscavenger N-acetyl cysteine significantly decreased the phosphorylation of ASK1 and HMME-induced apoptosis. Our results confirmed HMME cytotoxic effects in TNBCs via ROS-dependent activation of the Fas/FasL-ASK1-p38 axis.

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        Synthesis and Biological Evaluation of Novel Pyrazoline Derivatives as Anti-inflammatory and Antioxidant Agents

        Nadia A. Khalil,Eman M. Ahmed,Hala B. El-Nassan,Osama K. Ahmed,Ahmed M. Al-Abd 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

        A series of novel 5-aryl-3-cyclopropyl-4,5-dihydropyrazole derivatives 2a-p were synthesized via cyclization of chalcones 1a-h with thiosemicarbazide or semicarbazide HCl and evaluated as anti-inflammatory/antioxidant agents. The structures were confirmed by elemental analyses and spectral data. The free radical scavenging activity toward superoxide was determined. Their effect on hepatocytes viability and nitric oxide (NO) production in LPS-stimulated macrophages was also determined. The results showed that compounds 2e and 2n demonstrated the highest free-radical scavenging and anti-inflammatory activities, thus can be useful in the prevention of oxidative stress and inflammation-related disorders.

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