Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells.
Muhammed Ashiq ThalappilElena ButturiniAlessandra Carcereri de PratiIlaria BettinLorenzo AntoniniFilippo Umberto SapienzaStefania GarzoliRino RagnoSofia MariottoPublished in: Molecules (Basel, Switzerland) (2022)
Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N -acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy.
Keyphrases
- cell death
- cell proliferation
- combination therapy
- oxidative stress
- reactive oxygen species
- dna damage
- flow cytometry
- cell cycle arrest
- induced apoptosis
- cell migration
- endothelial cells
- diabetic rats
- high throughput
- transcription factor
- mass spectrometry
- squamous cell carcinoma
- bone marrow
- poor prognosis
- locally advanced
- essential oil
- high glucose
- gene expression
- wound healing
- rectal cancer
- high resolution
- heat shock protein
- radiation therapy
- genome wide analysis
- cell therapy
- sensitive detection