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Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis

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Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35712, Egypt
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Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
*
Author to whom correspondence should be addressed.
Academic Editor: Murali Mohan Yallapu
Sci. Pharm. 2022, 90(3), 42; https://doi.org/10.3390/scipharm90030042
Received: 6 May 2022 / Revised: 7 June 2022 / Accepted: 14 June 2022 / Published: 7 July 2022
Sitagliptin (STG) is a highly selective dipeptidyl peptidase-4 inhibitor recently used in the treatment of type 2 diabetes. The current study aimed to investigate the anti-neoplastic effect of STG alone and in combination with Doxorubicin (Dox), a known chemotherapeutic agent but with ominous side effects. After intramuscular inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice were divided into tumor-bearing control, STG-treated, Dox-treated, and a combination of STG and Dox-treated groups. The results showed a significant reduction in the tumor growth of the treated animals in comparison with those of the positive control group with a more prominent effect in the co-treated group. Where, the anti-proliferative and apoptotic effect of STG, and its chemo-sensitizing ability, when used in combination with Dox, was mediated by modulation of oxidative stress (MDA and GSH), attenuation of tumor inflammation (IL-6 and IL-1β), and angiogenesis (VEGF), suppressing proliferation (β-catenin and cyclin-D1) and enhancement of apoptosis (survivin, p53, caspase 3). Thus, in conclusion, STG as adjunctive therapy for Dox could be a strategy for the treatment of breast cancer patients, by their ability in hindering cell proliferation and minimizing the associated oxidative and inflammatory adverse reactions. View Full-Text
Keywords: Ehrlich solid carcinoma; sitagliptin; doxorubicin; β-catenin; cyclin-D1; survivin Ehrlich solid carcinoma; sitagliptin; doxorubicin; β-catenin; cyclin-D1; survivin
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MDPI and ACS Style

Salama, M.M.; Zaghloul, R.A.; Khalil, R.M.; El-Shishtawy, M.M. Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis. Sci. Pharm. 2022, 90, 42. https://doi.org/10.3390/scipharm90030042

AMA Style

Salama MM, Zaghloul RA, Khalil RM, El-Shishtawy MM. Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis. Scientia Pharmaceutica. 2022; 90(3):42. https://doi.org/10.3390/scipharm90030042

Chicago/Turabian Style

Salama, Mohamed M., Randa A. Zaghloul, Rania M. Khalil, and Mamdouh M. El-Shishtawy. 2022. "Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis" Scientia Pharmaceutica 90, no. 3: 42. https://doi.org/10.3390/scipharm90030042

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