دورية أكاديمية
أعرض في EDS

Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application.

التفاصيل البيبلوغرافية
العنوان: Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application.
المؤلفون: Abdelhamid AM; Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt., Saber S; Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt. Electronic address: sampharm81@gmail.com., Youssef ME; Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt., Gaafar AGA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, Egypt., Eissa H; Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Abd-Eldayem MA; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University, New Damietta, Egypt., Alqarni M; Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia., Batiha GE; Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt., Obaidullah AJ; Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Shahien MA; Department of Clinical Pharmacology, Faculty of Medicine, Damietta University, Damietta, Egypt., El-Ahwany E; Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt., Amin NA; Department of Hematology, Theodor Bilharz Research Institute, Giza, Egypt., Etman MA; Research and Development, Department of Drug Stability, Safe Pharma, Pharco Pharmaceuticals, Alexandria, Egypt., Kaddah MMY; Pharmaceutical and Fermentation Industries Development Center, City of Scientific Research and Technological Applications, New Borg El-Arab 21934, Alexandria, Egypt., Abd El-Fattah EE; Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
المصدر: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Jan; Vol. 145, pp. 112455. Date of Electronic Publication: 2021 Nov 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE
أسماء مطبوعة: Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
مواضيع طبية MeSH: Carcinoma, Hepatocellular*/drug therapy , Carcinoma, Hepatocellular*/metabolism , Carcinoma, Hepatocellular*/pathology , Liver Neoplasms*/drug therapy , Liver Neoplasms*/metabolism , Liver Neoplasms*/pathology, Benzhydryl Compounds/*pharmacology , Glucosides/*pharmacology , Metformin/*pharmacology , Neovascularization, Pathologic/*drug therapy , Signal Transduction/*drug effects, Animals ; Apoptosis/drug effects ; Autophagy/drug effects ; Disease Progression ; Hypoglycemic Agents/pharmacology ; MAP Kinase Kinase Kinases/metabolism ; Mice ; NF-kappa B/metabolism ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology
مستخلص: Hepatocellular carcinoma (HCC) is on the rise worldwide, and its incidence in diabetic patients is two to three times that of non-diabetics. Current therapeutic options fail to provide considerable survival benefits to patients with HCC. There is a strong possibility that the FDA-approved antidiabetic combination of empagliflozin and metformin could show complementary effects to control HCC progression. However, their multitarget effects have not yet been studied on HCC development. Therefore, the present study aims to evaluate the antitumorigenic activity of this combination in non-diabetic mice with diethylnitrosamine-induced HCC. Empagliflozin/metformin combination prolonged survival and improved histological features of mice livers. Additionally, Empagliflozin/metformin showed anti-inflammatory potential and relieved oxidative stress. On the one hand these effects are likely attributed to the ability of metformin to inactivate NF-κB in an AMPK-dependent mechanism and on the other hand to the ability of the empagliflozin to inhibit the MAPKs, p38 and ERK1/2. Empagliflozin also showed a less robust effect on AMPK than that of metformin. Moreover, empagliflozin enhanced the autophagy inducing activity of metformin. Furthermore, empagliflozin/metformin exhibited increased apoptotic potential. Consequently, empagliflozin augmented the antitumorigenic function of metformin by exerting better control of angiogenesis, and metastasis. To conclude, our findings suggest empagliflozin as an ideal adjunct to metformin for the inhibition of HCC progression. In addition, since the incidence of hypoglycemia is minimal due to insulin-independent mechanism of action of both treatments, empagliflozin/metformin could be a promising therapeutic modality for the management of diabetic patients with HCC; and even non diabetic ones.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
فهرسة مساهمة: Keywords: Angiogenesis; Apoptosis; Autophagy; Emagliflozin/metformin; Hepatocellular carcinoma; Metastasis
المشرفين على المادة: 0 (Benzhydryl Compounds)
0 (Glucosides)
0 (Hypoglycemic Agents)
0 (NF-kappa B)
0 (Sodium-Glucose Transporter 2 Inhibitors)
9100L32L2N (Metformin)
EC 2.7.11.25 (MAP Kinase Kinase Kinases)
HDC1R2M35U (empagliflozin)
تواريخ الأحداث: Date Created: 20211129 Date Completed: 20220309 Latest Revision: 20220309
رمز التحديث: 20231215
DOI: 10.1016/j.biopha.2021.112455
PMID: 34844106
قاعدة البيانات: MEDLINE
الوصف
تدمد:1950-6007
DOI:10.1016/j.biopha.2021.112455