Abstract
Background:
Several studies have revealed that abnormal activation of Notch signaling is closely
related with the development and progression of prostate cancer. Although there are numerous therapeutic
strategies, a more effective modality with least side effects is urgently required for the treatment of prostate
cancer. Carvacrol is a monoterpenoid phenol and majorly present in the essential oils of Lamiaceae family
plants. Many previous reports have shown various biological activities of carvacrol like antioxidant, antiinflammatory
and anticancer properties. Recently, we have shown potent anticancer property of carvacrol
against prostate cancer cell line DU145. In the current study, we report the chemopreventive and therapeutic
potential of carvacrol against another prostate cancer cell line PC-3 with its detailed mechanism of action.
Methods:
To determine the effect of the carvacrol on prostate cancer cells, the cell viability was estimated by
MTT assay and cell death was estimated by LDH release assay. The apoptotic assay was performed by DAPI
staining and FITC-Annexin V assay. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Cell
cycle analysis was performed by flow cytometry. Gene expression analysis was performed by quantitative real
time PCR.
Results:
Our results suggested that the carvacrol treatment significantly reduced the cell viability of PC-3 cells
in a dose- and time-dependent manner. The antiproliferative action of carvacrol was correlated with apoptosis
which was confirmed by nuclear condensation, FITC-Annexin V assay, modulation in expression of Bax, Bcl-2
and caspase activation. The mechanistic insight into carvacrol-induced apoptosis leads to finding of elevated
level of Reactive Oxygen Species (ROS) and mitochondrial membrane potential disruption. Cell cycle analysis
revealed that carvacrol prevented cell cycle in G0/G1 that was associated with decline in expression of cyclin D1
and Cyclin-Dependent Kinase 4 (CDK4) and augmented expression of CDK inhibitor p21. Having been said the
role of hyperactivation of Notch signaling in prostate cancer, we also deciphered that carvacrol could inhibit
Notch signaling in PC-3 cells via downregulation of Notch-1, and Jagged-1.
Conclusion:
Thus, our previous and current findings have established the strong potential of carvacrol as a
chemopreventive agent against androgen-independent human prostate cancer cells.