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

Abstract

Departmental sources 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/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 IC 50 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.

Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p

“…NSCLC is responsible for poor survival of a majority of lung cancer patients [16]. Due to non-specific symptoms and no effectual diagnostic tests, approximately 70% of NSCLC are diagnosed at an advanced stage [17]. Non-invasive prognostic biomarkers are needed for the diagnosis of the advanced NSCLC patients with different histological types [18].…”

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

“…PI3K primarily phosphorylates PIP2 to yield PIP3 and then activates AKT. Activated AKT can cause a series of phosphorylation cascade reactions and regulate vital downstream effector molecules, like mTOR to exert its biological effect (Dirk et al, 2018;Li et al, 2019). PI3K/AKT/mTOR signaling pathway controls cell growth, proliferation, cell polarity and cytoskeleton, and EMT and angiogenesis (Peng et al, 2014;Arash and Amirhossein, 2017;Falguni et al, 2018).…”

Inhibition of Non-Small Cell Lung Cancer Proliferation and Survival by Rosemary Extract Is Associated with Activation of ERK and AMPK

“…A search of the literature revealed studies indicating the predominant presence of the polyphenols rosmarinic acid (RA) and carnosic acid (CA) in RE [7]. In addition we found studies pointing to anticancer properties of RA and CA when used alone in in vitro models of NSCLC [66,67]. The potent anticancer effects seen with RE treatment could be attributed to CA, RA or any of the many chemicals present in RE each acting alone or in combination/synergistically.…”