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

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 diterp...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-03, Vol.14 (3), p.230
Main Authors: El-Huneidi, Waseem, Bajbouj, Khuloud, Muhammad, Jibran Sualeh, Vinod, Arya, Shafarin, Jasmin, Khoder, Ghalia, Saleh, Mohamed A, Taneera, Jalal, Abu-Gharbieh, Eman
Format: Article
Language:English
Subjects:
Acids
Akt
Apoptosis
Breast cancer
carnosic acid
caspase
Cell cycle
Cell growth
Cervical cancer
Estrogens
Flow cytometry
Gastric cancer
Kinases
Liver cancer
Medical prognosis
mTOR
Neuroblastoma
Prostate cancer
Proteins
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Summary: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 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.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph14030230