Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent due to its selective killing on cancer cells while sparing the normal cells. Nevertheless, breast adenocarcinoma cells can develop TRAIL resistance. Therefore, this project investigated the anti-...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-09-01
|
Series: | Heliyon |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844019361286 |
id |
doaj-2f7f255bd1c0430282b647103b427b54 |
---|---|
record_format |
Article |
spelling |
doaj-2f7f255bd1c0430282b647103b427b542020-11-25T02:04:55ZengElsevierHeliyon2405-84402019-09-0159e02468Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosisWei Yang Kong0Zong Yang Yee1Chun Wai Mai2Chee-Mun Fang3Syahril Abdullah4Siew Ching Ngai5School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, Semenyih, 43500, MalaysiaSchool of Post-Graduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, MalaysiaSchool of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia; Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, MalaysiaDivision of Biomedical Sciences, School of Pharmacy, University of Nottingham Malaysia, Jalan Broga, Semenyih, 43500, MalaysiaMedical Genetics Laboratory, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, 43400, Malaysia; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Selangor, 43400, MalaysiaSchool of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, Semenyih, 43500, Malaysia; Corresponding author.Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent due to its selective killing on cancer cells while sparing the normal cells. Nevertheless, breast adenocarcinoma cells can develop TRAIL resistance. Therefore, this project investigated the anti-cancer effects of the combination of epigenetic drugs zebularine and trichostatin A (ZT) with TRAIL (TZT) on the human breast adenocarcinoma cells. This treatment regimen was compared with the natural anti-cancer compound curcumin (Cur) and standard chemotherapeutic drug doxorubicin (Dox). As compared to TRAIL treatment, TZT treatment hampered the cell viability of human breast adenocarcinoma cells MDA-MB-231 significantly but not MCF-7 and immortalized non-cancerous human breast epithelial cells MCF10A. Unlike TZT, Cur and Dox treatments reduced cell viability in both human breast adenocarcinoma and epithelial cells significantly. Nevertheless, there were no changes in cell cycle in both TRAIL and TZT treatments in breast adenocarcinoma and normal epithelial cells. Intriguingly, Cur and Dox treatment generally induced G2/M arrest in MDA-MB-231, MCF-7 and MCF10A but Cur induced S phase arrest in MCF10A. The features of apoptosis such as morphological changes, apoptotic activity and the expression of cleaved poly (ADP) ribose polymerase (PARP) protein were more prominent in TRAIL and TZT-treated MDA-MB-231 as compared to MCF10A at 24 h post-treatment. Compared to TZT treatment, Cur and Dox treatments exhibited lesser apoptotic features in MDA-MB-231. Collectively, the sensitization using Zeb and TSA to augment TRAIL-induced apoptosis might be an alternative therapy towards human breast adenocarcinoma cells, without harming the normal human breast epithelial cells.http://www.sciencedirect.com/science/article/pii/S2405844019361286Cell biologyEpigeneticsCancer researchTumour necrosis factor-related apoptosis inducing ligand (TRAIL)ZebularineTrichostatin A |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Yang Kong Zong Yang Yee Chun Wai Mai Chee-Mun Fang Syahril Abdullah Siew Ching Ngai |
spellingShingle |
Wei Yang Kong Zong Yang Yee Chun Wai Mai Chee-Mun Fang Syahril Abdullah Siew Ching Ngai Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis Heliyon Cell biology Epigenetics Cancer research Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) Zebularine Trichostatin A |
author_facet |
Wei Yang Kong Zong Yang Yee Chun Wai Mai Chee-Mun Fang Syahril Abdullah Siew Ching Ngai |
author_sort |
Wei Yang Kong |
title |
Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis |
title_short |
Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis |
title_full |
Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis |
title_fullStr |
Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis |
title_full_unstemmed |
Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis |
title_sort |
zebularine and trichostatin a sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (trail)-induced apoptosis |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2019-09-01 |
description |
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent due to its selective killing on cancer cells while sparing the normal cells. Nevertheless, breast adenocarcinoma cells can develop TRAIL resistance. Therefore, this project investigated the anti-cancer effects of the combination of epigenetic drugs zebularine and trichostatin A (ZT) with TRAIL (TZT) on the human breast adenocarcinoma cells. This treatment regimen was compared with the natural anti-cancer compound curcumin (Cur) and standard chemotherapeutic drug doxorubicin (Dox). As compared to TRAIL treatment, TZT treatment hampered the cell viability of human breast adenocarcinoma cells MDA-MB-231 significantly but not MCF-7 and immortalized non-cancerous human breast epithelial cells MCF10A. Unlike TZT, Cur and Dox treatments reduced cell viability in both human breast adenocarcinoma and epithelial cells significantly. Nevertheless, there were no changes in cell cycle in both TRAIL and TZT treatments in breast adenocarcinoma and normal epithelial cells. Intriguingly, Cur and Dox treatment generally induced G2/M arrest in MDA-MB-231, MCF-7 and MCF10A but Cur induced S phase arrest in MCF10A. The features of apoptosis such as morphological changes, apoptotic activity and the expression of cleaved poly (ADP) ribose polymerase (PARP) protein were more prominent in TRAIL and TZT-treated MDA-MB-231 as compared to MCF10A at 24 h post-treatment. Compared to TZT treatment, Cur and Dox treatments exhibited lesser apoptotic features in MDA-MB-231. Collectively, the sensitization using Zeb and TSA to augment TRAIL-induced apoptosis might be an alternative therapy towards human breast adenocarcinoma cells, without harming the normal human breast epithelial cells. |
topic |
Cell biology Epigenetics Cancer research Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) Zebularine Trichostatin A |
url |
http://www.sciencedirect.com/science/article/pii/S2405844019361286 |
work_keys_str_mv |
AT weiyangkong zebularineandtrichostatinasensitizedhumanbreastadenocarcinomacellstowardstumornecrosisfactorrelatedapoptosisinducingligandtrailinducedapoptosis AT zongyangyee zebularineandtrichostatinasensitizedhumanbreastadenocarcinomacellstowardstumornecrosisfactorrelatedapoptosisinducingligandtrailinducedapoptosis AT chunwaimai zebularineandtrichostatinasensitizedhumanbreastadenocarcinomacellstowardstumornecrosisfactorrelatedapoptosisinducingligandtrailinducedapoptosis AT cheemunfang zebularineandtrichostatinasensitizedhumanbreastadenocarcinomacellstowardstumornecrosisfactorrelatedapoptosisinducingligandtrailinducedapoptosis AT syahrilabdullah zebularineandtrichostatinasensitizedhumanbreastadenocarcinomacellstowardstumornecrosisfactorrelatedapoptosisinducingligandtrailinducedapoptosis AT siewchingngai zebularineandtrichostatinasensitizedhumanbreastadenocarcinomacellstowardstumornecrosisfactorrelatedapoptosisinducingligandtrailinducedapoptosis |
_version_ |
1724940400134717440 |