Abstract
Lung cancer is one of the leading causes of cancer-related mortality worldwide. Although effective clinical drugs for treating advanced stages are available, interest in alternative herbal medicines has gained momentum. Herbal extracts are potent antioxidants that reportedly inhibit the growth of various cancer cell lines. In the present study, we investigated the effects of essential oils and hexane, methanolic, and aqueous extracts, obtained from various parts (bark, needles, and pollen) of Pinus eldarica against human lung cancer (A549) cells. First, the DPPH radical scavenging activities of P. eldarica extracts and essential oils were examined, which revealed that methanolic extracts presented higher antioxidant activity than the other extracts and essential oils. Next, A549 cells were exposed to various concentrations of the extracts and essential oils for 48 h. P. eldarica extracts/essential oil-treated lung cancer cells demonstrated a significant decrease in cell proliferation, along with an induction of apoptotic cell death, particularly, the pollen hexane extract, bark essential oil, and methanolic needle extract showed superior results, with IC50 values of 31.7, 17.9, and 0.3 μg/mL, respectively. In the cell cycle analysis, treatment of A549 cells with the methanolic needle and pollen hexane extracts led to apoptosis and accumulation of cells in the sub-G1 phase. Further, exposure to the bark essential oil and methanolic needle extract decreased the cell population in the G2/M phase. Notably, treatment with the pollen hexane extract, bark essential oil, and methanolic needle extract resulted in caspase-3 activation, poly (ADP-ribose) polymerase cleavage, Bcl-2 downregulation, and Bax and p53 regulation in A549 cells. Furthermore, these extracts and essential oils decreased the migration, and colony formation of A549 cells. These findings provide experimental evidence for a new therapeutic effect of P. eldarica against human lung cancer and suggest P. eldarica as a potential chemopreventive natural resource for developing novel cancer therapeutics.
Highlights
We aimed to evaluate the antioxidant, cytotoxic, and proapoptotic effects of hexane, methanolic, and aqueous extracts, and essential oils, of various parts of P. eldarica on lung cancer (A549) cells, with the possible elucidation of cellular and molecular mechanisms
The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was performed to determine the antioxidant activity of extracts and essential oils obtained from the various parts of P. eldarica (Figure 1)
poly (ADP-ribose) polymerase (PARP) in A549 cells treated with IC50 concentrations of the pollen hexane extract, bark essential oil, and methanolic needle extract. These results suggest that activation of the caspase pathway is essential for inducing apoptosis in A549 cells following treatment with
Summary
Cancer is a term that encompasses a large family of diseases in which abnormal cells undergo uncontrolled division and can spread to other tissues through the blood creativecommons.org/licenses/by/ 4.0/). Lung cancer is the most commonly diagnosed cancer (11.6% of all cases), ranking first in terms of reported cancer deaths (18.4% of all cancer deaths) [1]. Throughout the history of human life, natural products derived from living organisms such as plants have been utilized as a primary source of medicinal agents [2]. Plants provide an extensive reservoir of therapeutic agents, representing a significant structural variety and remarkable chemical entities in modern medicine. Numerous studies have reported that natural products derived from plants possess anticancer properties [3]
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