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Article

Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines

1
Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
2
Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
3
Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
4
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
5
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 33516, Egypt
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2021, 14(3), 230; https://doi.org/10.3390/ph14030230
Submission received: 8 February 2021 / Revised: 23 February 2021 / Accepted: 3 March 2021 / Published: 8 March 2021
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

Abstract

Gastric cancer is among the most common malignancies worldwide. Due to limited availability of therapeutic options, there is a constant need to find new therapies that could target advanced, recurrent, and metastatic gastric cancer. Carnosic acid is a naturally occurring polyphenolic abietane diterpene derived from Rosmarinus officinalis and reported to have numerous pharmacological effects. In this study, the cytotoxicity assay, Annexin V-FITC/PI, caspases 3, 8, and 9, cell cycle analysis, and Western blotting were used to assess the effect of carnosic acid on the growth and survival of human gastric cancer cell lines (AGS and MKN-45). Our findings showed that carnosic acid inhibited human gastric cancer cell proliferation and survival in a dose-dependent manner. Additionally, carnosic acid is found to inhibit the phosphorylation/activation of Akt and mTOR. Moreover, carnosic acid enhanced the cleavage of PARP and downregulated survivin expression, both being known markers of apoptosis. In conclusion, carnosic acid exhibits antitumor activity against human gastric cancer cells via modulating the Akt-mTOR signaling pathway that plays a crucial role in gastric cancer cell proliferation and survival.
Keywords: carnosic acid; gastric cancer; apoptosis; Akt; mTOR; caspase; PARP; survivin carnosic acid; gastric cancer; apoptosis; Akt; mTOR; caspase; PARP; survivin

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MDPI and ACS Style

El-Huneidi, W.; Bajbouj, K.; Muhammad, J.S.; Vinod, A.; Shafarin, J.; Khoder, G.; Saleh, M.A.; Taneera, J.; Abu-Gharbieh, E. Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines. Pharmaceuticals 2021, 14, 230. https://doi.org/10.3390/ph14030230

AMA Style

El-Huneidi W, Bajbouj K, Muhammad JS, Vinod A, Shafarin J, Khoder G, Saleh MA, Taneera J, Abu-Gharbieh E. Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines. Pharmaceuticals. 2021; 14(3):230. https://doi.org/10.3390/ph14030230

Chicago/Turabian Style

El-Huneidi, Waseem, Khuloud Bajbouj, Jibran Sualeh Muhammad, Arya Vinod, Jasmin Shafarin, Ghalia Khoder, Mohamed A. Saleh, Jalal Taneera, and Eman Abu-Gharbieh. 2021. "Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines" Pharmaceuticals 14, no. 3: 230. https://doi.org/10.3390/ph14030230

APA Style

El-Huneidi, W., Bajbouj, K., Muhammad, J. S., Vinod, A., Shafarin, J., Khoder, G., Saleh, M. A., Taneera, J., & Abu-Gharbieh, E. (2021). Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines. Pharmaceuticals, 14(3), 230. https://doi.org/10.3390/ph14030230

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