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Published on: January 26, 2019
Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage
Hurng-Wern Huang1, Jen-Yang Tang2,3, Fu Ou-Yang4,5
1Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. sting@mail.nsysu.edu.tw.
Abstract:
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 N-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.
Insights
The marine compound sinularin selectively kills breast cancer cells by inducing cell cycle arrest, apoptosis, and DNA damage. This natural product shows promise as a targeted cancer therapy.
Area of Science:
- Marine Natural Products
- Cancer Biology
- Cellular Mechanisms
Background:
- Sinularin, a compound from marine soft corals, exhibits antiproliferative effects against various cancers.
- The selective cancer-killing potential of sinularin remains underexplored.
Purpose of the Study:
- To investigate the selective killing effects of sinularin on breast cancer cells.
- To elucidate the underlying mechanisms of sinularin-induced cancer cell death.
Main Methods:
- Cell viability assays (MTS) comparing cancer and normal breast cells.
- Flow cytometry for cell cycle analysis (7-AAD) and apoptosis (Annexin V/7-AAD).
- Western blotting for apoptosis markers (PARP, caspases) and oxidative stress indicators (ROS, 8-oxodG).
Main Results:
- Sinularin dose-responsively reduced breast cancer cell viability while sparing normal cells.
- Induced G2/M cell cycle arrest and apoptosis in SKBR3 cells.
- Triggered oxidative stress, DNA damage, and caspase activation, which were partially inhibited by N-acetylcysteine (NAC).
Conclusions:
- Sinularin demonstrates selective killing of breast cancer cells.
- Mechanisms include G2/M arrest, apoptosis induction, and oxidative DNA damage.
- Sinularin represents a potential therapeutic agent for breast cancer treatment.
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