Abstract:
Cedrus libani, a member of the genus Cedar and family Pinaceae, is frequently used in
traditional Lebanese medicine to treat several ailments. Essential oils extracted from this
plant were found to exhibit important biomedical properties, including anti-ulcerogenic,
anti-viral, neuroprotective as well as anti-proliferative activity. The present study aims to
isolate himachalol, a major compound in the wood oil extract, and assess its anticancer
activity against skin (B16F-10), brain (SF-268), colorectal (Caco-2 and HT-29) and
ovarian (Sk-OV-3) cancer cells. 2-himachalen-7-ol (7-HC) was isolated using silica gel
column chromatography, identified using GC-MS and confirmed with NMR studies.
Cytotoxicity assays were performed using WST proliferation kit. Cell cycle analysis and
cell apoptosis were evaluated using flow cytometry. The level of Akt, Erk, Bax and Bcl-2 proteins were determined via western blot analysis. Data revealed that 7-HC exhibits
potent anti-proliferative activities against most treated cells, with B16F-10 being the most
sensitive and Sk-OV-3 the least sensitive. Flow cytometry analysis demonstrated that the
cytotoxicity of 7-HC is mediated via arresting the cell at Sub-G1 and inducing cell death
via late apoptosis. Western blot analysis showed that treatment with 7-HC causes a downregulation
of the level of anti-apoptotic proteins (Bcl-2) and an up-regulation of the level
of pro-apoptotic proteins (Bax). A decline in the level of phosphorylated Erk and Akt was
also noted. In conclusion, the current study revealed that 7-HC has a remarkable anticancer activity against a panel of cancer cell lines, an effect that may be partly attributed to the
inhibition of the PI3K/Akt and MAPK/Erk pathways.
