Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage

The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In...

Full description

Saved in:
Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2018-04, Vol.23 (4), p.849
Main Authors: Huang, Hurng-Wern, Tang, Jen-Yang, Ou-Yang, Fu, Wang, Hui-Ru, Guan, Pei-Ying, Huang, Chiung-Yao, Chen, Chung-Yi, Hou, Ming-Feng, Sheu, Jyh-Horng, Chang, Hsueh-Wei
Format: Article
Language:English
Subjects:
Acetylcysteine
Adenosine diphosphate
Annexin V
Apoptosis
Breast cancer
Corals
Deoxyguanosine
Deoxyribonucleic acid
DNA
DNA damage
Flow cytometry
marine natural product
Membrane potential
Mitochondria
Oxidative stress
Poly(ADP-ribose)
Poly(ADP-ribose) polymerase
Pretreatment
Reactive oxygen species
Ribose
SKBR3
soft coral
Superoxide
Western blotting
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium, inner salt (MTS) assay, sinularin dose-responsively decreased the cell viability of two breast cancer (SKBR3 and MDA-MB-231) cells, but showed less effect on breast normal (M10) cells after a 24 h treatment. According to 7-aminoactinomycin D (7AAD) flow cytometry, sinularin dose-responsively induced the G2/M cycle arrest of SKBR3 cells. Sinularin dose-responsively induced apoptosis on SKBR3 cells in terms of a flow cytometry-based annexin V/7AAD assay and pancaspase activity, as well as Western blotting for cleaved forms of poly(ADP-ribose) polymerase (PARP), caspases 3, 8, and 9. These caspases and PARP activations were suppressed by -acetylcysteine (NAC) pretreatment. Moreover, sinularin dose-responsively induced oxidative stress and DNA damage according to flow cytometry analyses of reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), mitochondrial superoxide, and 8-oxo-2'-deoxyguanosine (8-oxodG)). In conclusion, sinularin induces selective killing, G2/M arrest, apoptosis, and oxidative DNA damage of breast cancer cells.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules23040849