Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines

Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninon...

Full description

Bibliographic Details
Main Authors:	Babak Esmaeelian, Kirsten Benkendorff, Catherine A. Abbott, Martin R. Johnston
Format:	Article
Language:	English
Published:	MDPI AG 2013-10-01
Series:	Marine Drugs
Subjects:	colorectal cancer apoptosis marine mollusc brominated indoles
Online Access:	http://www.mdpi.com/1660-3397/11/10/3802

id	doaj-615e7664436d4672ab176e354d9a6de8
record_format	Article
spelling	doaj-615e7664436d4672ab176e354d9a6de82020-11-24T23:08:20ZengMDPI AGMarine Drugs1660-33972013-10-0111103802382210.3390/md11103802Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell LinesBabak EsmaeelianKirsten BenkendorffCatherine A. AbbottMartin R. JohnstonDicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and 1H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC50 = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC50 = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer.http://www.mdpi.com/1660-3397/11/10/3802colorectal cancerapoptosismarine molluscbrominated indoles
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Babak Esmaeelian Kirsten Benkendorff Catherine A. Abbott Martin R. Johnston
spellingShingle	Babak Esmaeelian Kirsten Benkendorff Catherine A. Abbott Martin R. Johnston Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines Marine Drugs colorectal cancer apoptosis marine mollusc brominated indoles
author_facet	Babak Esmaeelian Kirsten Benkendorff Catherine A. Abbott Martin R. Johnston
author_sort	Babak Esmaeelian
title	Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines
title_short	Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines
title_full	Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines
title_fullStr	Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines
title_full_unstemmed	Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines
title_sort	purified brominated indole derivatives from dicathais orbita induce apoptosis and cell cycle arrest in colorectal cancer cell lines
publisher	MDPI AG
series	Marine Drugs
issn	1660-3397
publishDate	2013-10-01
description	Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and 1H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC50 = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC50 = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer.
topic	colorectal cancer apoptosis marine mollusc brominated indoles
url	http://www.mdpi.com/1660-3397/11/10/3802
work_keys_str_mv	AT babakesmaeelian purifiedbrominatedindolederivativesfromdicathaisorbitainduceapoptosisandcellcyclearrestincolorectalcancercelllines AT kirstenbenkendorff purifiedbrominatedindolederivativesfromdicathaisorbitainduceapoptosisandcellcyclearrestincolorectalcancercelllines AT catherineaabbott purifiedbrominatedindolederivativesfromdicathaisorbitainduceapoptosisandcellcyclearrestincolorectalcancercelllines AT martinrjohnston purifiedbrominatedindolederivativesfromdicathaisorbitainduceapoptosisandcellcyclearrestincolorectalcancercelllines
_version_	1725614785557430272

Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines

Similar Items