Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells

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 va...

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Main Authors: Tayyebeh Ghaffari, Solmaz Asnaashari, Ebrahim Irannejad, Abbas Delazar, Safar Farajnia, Joo-Hyun Hong, Changhyun Pang, Hamed Hamishehkar, Ki Hyun Kim
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/11/13/5763
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author Tayyebeh Ghaffari
Solmaz Asnaashari
Ebrahim Irannejad
Abbas Delazar
Safar Farajnia
Joo-Hyun Hong
Changhyun Pang
Hamed Hamishehkar
Ki Hyun Kim
author_facet Tayyebeh Ghaffari
Solmaz Asnaashari
Ebrahim Irannejad
Abbas Delazar
Safar Farajnia
Joo-Hyun Hong
Changhyun Pang
Hamed Hamishehkar
Ki Hyun Kim
author_sort Tayyebeh Ghaffari
collection DOAJ
description 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 <i>Pinus eldarica</i> against human lung cancer (A549) cells. First, the DPPH radical scavenging activities of <i>P. eldarica</i> 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. <i>P. eldarica</i> 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 IC<sub>50</sub> 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 <i>P. eldarica</i> against human lung cancer and suggest <i>P. eldarica</i> as a potential chemopreventive natural resource for developing novel cancer therapeutics.
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spelling doaj.art-318c8b62cd9945359edb04da743fd9062023-11-22T01:08:46ZengMDPI AGApplied Sciences2076-34172021-06-011113576310.3390/app11135763Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer CellsTayyebeh Ghaffari0Solmaz Asnaashari1Ebrahim Irannejad2Abbas Delazar3Safar Farajnia4Joo-Hyun Hong5Changhyun Pang6Hamed Hamishehkar7Ki Hyun Kim8Drug Applied Research Center, Student Research Committee, Tabriz University of Medical Sciences, Tabriz P.O. Box 51656-65811, IranBiotechnology Research Center, Tabriz University of Medical Sciences, Tabriz P.O. Box 51656-65811, IranFaculty Member of Academic Center for Education, Culture and Research (ACECR), Tabriz P.O. Box 51656-65811, IranPharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz P.O. Box 51656-65811, IranDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz P.O. Box 51656-65811, IranSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Chemical Engineering, Sungkyunkwan University, Suwon 16419, KoreaDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz P.O. Box 51656-65811, IranSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaLung 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 <i>Pinus eldarica</i> against human lung cancer (A549) cells. First, the DPPH radical scavenging activities of <i>P. eldarica</i> 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. <i>P. eldarica</i> 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 IC<sub>50</sub> 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 <i>P. eldarica</i> against human lung cancer and suggest <i>P. eldarica</i> as a potential chemopreventive natural resource for developing novel cancer therapeutics.https://www.mdpi.com/2076-3417/11/13/5763<i>Pinus eldarica</i>lung cancerA549apoptosiscaspase-3PARP
spellingShingle Tayyebeh Ghaffari
Solmaz Asnaashari
Ebrahim Irannejad
Abbas Delazar
Safar Farajnia
Joo-Hyun Hong
Changhyun Pang
Hamed Hamishehkar
Ki Hyun Kim
Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells
Applied Sciences
<i>Pinus eldarica</i>
lung cancer
A549
apoptosis
caspase-3
PARP
title Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells
title_full Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells
title_fullStr Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells
title_full_unstemmed Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells
title_short Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of <i>Pinus eldarica</i> in Lung Cancer Cells
title_sort comparative evaluation of apoptosis induction using needles bark and pollen extracts and essential oils of i pinus eldarica i in lung cancer cells
topic <i>Pinus eldarica</i>
lung cancer
A549
apoptosis
caspase-3
PARP
url https://www.mdpi.com/2076-3417/11/13/5763
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