| Autor: |
Amrati, Fatima Ez-Zahra, Elmadbouh, Omer Hany Miligy, Chebaibi, Mohamed, Soufi, Badr, Conte, Raffaele, Slighoua, Meryem, Saleh, Asmaa, Al Kamaly, Omkulthom, Drioiche, Aziz, Zair, Touria, Edderkaoui, Mouad, Bousta, Dalila |
| Zdroj: |
Journal of Biomolecular Structure and Dynamics; November 2023, Vol. 41 Issue: 17 p8517-8534, 18p |
| Abstrakt: |
AbstractPancreatic adenocarcinoma is a disease with no effective treatment. Chemo-resistance contributes to the dismal prognosis for patients diagnosed with the disease. This study aims to evaluate the toxicity and the effect of Caralluma europaea(C.E) extracts on cancer cell survival, apoptosis, chemo-resistance, and pro-cancer pathways, in pancreatic cancer. The acute and subacute toxicities of C.Eextracts were evaluated. The cytotoxic effect on pancreatic cancer cell survival and apoptosis was determined by MTT assay and DNA fragmentation. The expression of cancer stemness markers was measured using Western blot. A molecular docking was used to test the possible effects of C.Ecompounds in inhibiting the Hedgehog and activating caspase-3. The hydroethanolic extract’s DL50was over 5000 mg/kg. During the subacute toxicity, only saponins extract showed some hepatic toxicity signs. Cells treated with C.Eextracts combined with gemcitabine revealed an additive anti-survival activity. C.Eextracts sensitized resistant MIA-PaCa-2 to gemcitabine treatment. Most of the C.Eextracts downregulated the expression of cancer stemness-associated genes. Luteolin-7-O-glucoside presented the highest docking Gscore on human Smoothened. Isorhamnetin-3-O-rutinoside induced apoptosis via activation of caspase-3. C.Eextracts can be considered safe in inhibiting pancreatic cancer cell survival, inducing apoptosis, and sensitizing cells to chemotherapy viaHedgehog inhibition and caspase-3 activation.Communicated by Ramaswamy H. Sarma |
| Databáze: |
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