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.
Highlights
Worldwide, gastric cancer (GC) is considered to be one of the most common malignancies, leading to significant annual human cancer deaths [1]
ResultsTo investigate the effects of carnosic acid on gastric cancer cell proliferation, the AGS
MKN-45 cells were treated with increasing concentrations of carnosic acid
Summary
Gastric cancer (GC) is considered to be one of the most common malignancies, leading to significant annual human cancer deaths [1]. GC is the third largest cause of cancer-related deaths and is a global public health priority [2]. There is an urgent need to find novel and alternative therapies that could target gastric cancer. Secondary metabolites derived from natural sources, primarily herbal plants, with potential pharmacological properties and less toxicity could be used to synthesize novel pharmaceutical products [4]. Among these natural compounds are the ‘terpenes’ that have been reported to possess various anticancer pharmacological properties.
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