Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells
Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the stud...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/5/1240 |
| _version_ | 1828344418667593728 |
|---|---|
| author | Asvinidevi Arumugam Muhammad Din Ibrahim Saie Brindha Kntayya Nooraini Mohd Ain Renato Iori Stefania Galletti Costas Ioannides Ahmad Faizal Abdull Razis |
| author_facet | Asvinidevi Arumugam Muhammad Din Ibrahim Saie Brindha Kntayya Nooraini Mohd Ain Renato Iori Stefania Galletti Costas Ioannides Ahmad Faizal Abdull Razis |
| author_sort | Asvinidevi Arumugam |
| collection | DOAJ |
| description | Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC<sub>50</sub> values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G<sub>2</sub>/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent. |
| first_indexed | 2024-04-13T23:57:00Z |
| format | Article |
| id | doaj.art-e08e5d4450ff486ab4d8bfc4d440485d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T23:57:00Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e08e5d4450ff486ab4d8bfc4d440485d2022-12-22T02:23:51ZengMDPI AGMolecules1420-30492020-03-01255124010.3390/molecules25051240molecules25051240Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 CellsAsvinidevi Arumugam0Muhammad Din Ibrahim1Saie Brindha Kntayya2Nooraini Mohd Ain3Renato Iori4Stefania Galletti5Costas Ioannides6Ahmad Faizal Abdull Razis7UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, MalaysiaUPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, MalaysiaUPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, MalaysiaUPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, MalaysiaCREA Consiglio per la ricerca in agricoltura e l’analisi dell’economia agraria, Centro di Ricerca Agricoltura e Ambiente (CREA-AA), 40128 Bologna, ItalyCREA Consiglio per la ricerca in agricoltura e l’analisi dell’economia agraria, Centro di Ricerca Agricoltura e Ambiente (CREA-AA), 40128 Bologna, ItalyFaculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UKLaboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, MalaysiaGluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC<sub>50</sub> values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G<sub>2</sub>/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.https://www.mdpi.com/1420-3049/25/5/1240glucosinolategluconasturtiin-isothiocyanateapoptosiscancer chemoprevention |
| spellingShingle | Asvinidevi Arumugam Muhammad Din Ibrahim Saie Brindha Kntayya Nooraini Mohd Ain Renato Iori Stefania Galletti Costas Ioannides Ahmad Faizal Abdull Razis Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells Molecules glucosinolate gluconasturtiin-isothiocyanate apoptosis cancer chemoprevention |
| title | Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells |
| title_full | Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells |
| title_fullStr | Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells |
| title_full_unstemmed | Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells |
| title_short | Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells |
| title_sort | induction of apoptosis by gluconasturtiin isothiocyanate gnst itc in human hepatocarcinoma hepg2 cells and human breast adenocarcinoma mcf 7 cells |
| topic | glucosinolate gluconasturtiin-isothiocyanate apoptosis cancer chemoprevention |
| url | https://www.mdpi.com/1420-3049/25/5/1240 |
| work_keys_str_mv | AT asvinideviarumugam inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT muhammaddinibrahim inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT saiebrindhakntayya inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT noorainimohdain inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT renatoiori inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT stefaniagalletti inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT costasioannides inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells AT ahmadfaizalabdullrazis inductionofapoptosisbygluconasturtiinisothiocyanategnstitcinhumanhepatocarcinomahepg2cellsandhumanbreastadenocarcinomamcf7cells |