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

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.

Ethyl acetate extract of Nepenthes adrianii x clipeata induces antiproliferation, apoptosis, and DNA damage against oral cancer cells through oxidative stress

“…Based on these findings, EANA may be regarded as the ROS‐modulating agent. ROS‐modulating agents may display preferential killing against cancer cells by providing exogenous ROS, which may overload the ROS tolerance threshold of cancer cells and lead to cell death . However, normal cells have lower ROS basal level than cancer cells, tolerate this exogenous ROS, and lead to cell survival .…”

“…Apoptosis was examined by annexin V/7AAD double staining kit (Strong Biotech Corporation, Taipei, Taiwan) as previously described . Cells were incubated with annexin V‐labeled with fluorescein isothiocyanate/7AAD (10 and 1 μg/mL) for 30 minutes and performed flow cytometry (Accuri C6).…”

LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo

“…It is noted that LY303511 does not induce subG1 accumulation after 24 hours treatment although the apoptosis is inducible. Similarly, several anticancer agents such sulfonyl chromen‐4‐ones (CHW09), sinularin, and Gracilaria butanol extract show the apoptosis expression on oral and breast cancer cells in the absence of subG1 accumulation. It is possible that longer drug treatment time is required to accumulate subG1 population for some apoptosis‐inducible drugs.…”

“…Annexin V kit (Strong Biotech Corporation, Taipei, Taiwan) can detect the apoptosis by binding the inside out phosphatidylserine located at plasma membrane . Briefly, cells were treated with FITC‐labeled annexin V and 7AAD (10 and 1 μg/mL) for 30 minutes.…”

Sodium cantharidinate suppresses human osteosarcoma MG‑63 cell proliferation and induces cell cycle arrest by inhibition of PI3K/AKT activation

“…Apparently, MG-63 cells showed a decelerated proliferation between 24 and 72 h after 5.0 µM of SC treatment. Cell cycle arrest is closely related to inhibition of cell proliferation (28). Thus, FACS experiment was established to analyze cell cycle distribution after SC treatment.…”