In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells
Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
PeerJ Inc.
2017-07-01
|
Series: | PeerJ |
Subjects: | |
Online Access: | https://peerj.com/articles/3460.pdf |
_version_ | 1797417968034906112 |
---|---|
author | Aisha I. El habbash Najihah Mohd Hashim Mohamed Yousif Ibrahim Maizatulakmal Yahayu Fatima Abd Elmutaal Omer Mashitoh Abd Rahman Noraziah Nordin Gwendoline Ee Cheng Lian |
author_facet | Aisha I. El habbash Najihah Mohd Hashim Mohamed Yousif Ibrahim Maizatulakmal Yahayu Fatima Abd Elmutaal Omer Mashitoh Abd Rahman Noraziah Nordin Gwendoline Ee Cheng Lian |
author_sort | Aisha I. El habbash |
collection | DOAJ |
description | Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 ± 1.48 µM at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing. |
first_indexed | 2024-03-09T06:27:13Z |
format | Article |
id | doaj.art-bdd61b8925a648a0bc63d61d88083cbe |
institution | Directory Open Access Journal |
issn | 2167-8359 |
language | English |
last_indexed | 2024-03-09T06:27:13Z |
publishDate | 2017-07-01 |
publisher | PeerJ Inc. |
record_format | Article |
series | PeerJ |
spelling | doaj.art-bdd61b8925a648a0bc63d61d88083cbe2023-12-03T11:19:24ZengPeerJ Inc.PeerJ2167-83592017-07-015e346010.7717/peerj.3460In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cellsAisha I. El habbash0Najihah Mohd Hashim1Mohamed Yousif Ibrahim2Maizatulakmal Yahayu3Fatima Abd Elmutaal Omer4Mashitoh Abd Rahman5Noraziah Nordin6Gwendoline Ee Cheng Lian7Pharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaPharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaPharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaDepartment of Bioproduct Research & Innovation, Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia, Johor Bahru, MalaysiaPharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaPharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaPharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaDepartment of Chemistry, Faculty of Science, Universiti Putra Malaysia, Selangor, MalaysiaNatural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 ± 1.48 µM at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing.https://peerj.com/articles/3460.pdfAntitumorα-mangostinApoptosisHeLa |
spellingShingle | Aisha I. El habbash Najihah Mohd Hashim Mohamed Yousif Ibrahim Maizatulakmal Yahayu Fatima Abd Elmutaal Omer Mashitoh Abd Rahman Noraziah Nordin Gwendoline Ee Cheng Lian In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells PeerJ Antitumor α-mangostin Apoptosis HeLa |
title | In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells |
title_full | In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells |
title_fullStr | In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells |
title_full_unstemmed | In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells |
title_short | In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells |
title_sort | in vitro assessment of anti proliferative effect induced by α mangostin from cratoxylum arborescens on hela cells |
topic | Antitumor α-mangostin Apoptosis HeLa |
url | https://peerj.com/articles/3460.pdf |
work_keys_str_mv | AT aishaielhabbash invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT najihahmohdhashim invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT mohamedyousifibrahim invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT maizatulakmalyahayu invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT fatimaabdelmutaalomer invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT mashitohabdrahman invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT noraziahnordin invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells AT gwendolineeechenglian invitroassessmentofantiproliferativeeffectinducedbyamangostinfromcratoxylumarborescensonhelacells |