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21 October 2019 : Laboratory Research  

Antiproliferative Activity of Carnosic Acid is Mediated via Inhibition of Cell Migration and Invasion, and Suppression of Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Signaling Pathway

Liqun Zhao1BCD, Juanni Zhang2CDF, Yinke Fan3BCD, Ya Li4ACEG*

DOI: 10.12659/MSM.917735

Med Sci Monit 2019; 25:7864-7871

Abstract

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortalities worldwide and majority of these deaths result from non-small cell lung cancer (NSCLC). The primary objective of this research was to determine the anticancer potential of carnosic acid, a plant derived abietane diterpene, against human lung cancer cells, as well as to determine its effects on cell migration and invasion, apoptosis, and the PI3K/AKT/m-TOR signaling pathway.

MATERIAL AND METHODS: Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay; fluorescence microscopy using acridine orange/ethidium bromide stain and Comet assay were used to study cellular apoptosis. In vitro wound healing assay was used to study effects on cell migration; Transwell assay was used to study cell invasion after drug treatment. Western blot assay was used to study effects of carnosic acid on the PI3K/AKT/m-TOR signaling pathway.

RESULTS: It was shown that carnosic acid could inhibit the growth of A-549 human non-small cell lung carcinoma cells dose-dependently showing an IC₅₀ value of 12.5 μM. This growth inhibition of A-549 cells was mediated via apoptotic cell death as observed by fluorescence microscopy showing nuclear fragmentation and chromatin condensation. Carnosic acid, dose-dependently, also inhibited cell migration and invasion. Finally, western blot assay revealed that carnosic acid also led to inhibition of the PI3K/AKT/m-TOR signaling pathway.

CONCLUSIONS: In conclusion, our results showed that Carnosic acid has the potential to inhibit cancer cell growth in A-549 lung cancer cells by activating apoptotic death, inhibiting cell migration and invasion and suppressing PI3K/AKT/m-TOR signaling pathway.

Keywords: Apoptosis, Cell Migration Assays, Lung Neoplasms, Phosphatidylinositol 3-Kinases, A549 cells, Abietanes, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Cell Movement, Cell Proliferation, Cell Survival, China, Gene Expression Regulation, Neoplastic, Neoplasm Invasiveness, Phosphorylation, Proto-Oncogene Proteins c-akt, Signal Transduction, TOR Serine-Threonine Kinases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750