Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa.

BACKGROUND: Marine algae consumption is linked to law cancer incidences in countries that traditionally consume marine products. Hence, Phytochemicals are considered as potential chemo-preventive and chemotherapeutic agents against cancer. We investigated the effects of the algal sulfated polysaccharide extract (ASPE) from the red marine alga L. papillosa on MDA-MB-231 human breast cancer cell line. METHODS: Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. Changes in the expression of certain genes associated with cell cycle regulation was conducted by PCR real time analyses. Further investigations on apoptotic molecules was performed by ROS measurement and protein profiling. RESULTS: ASPE at low doses (10 µg/ml), inhibited cell proliferation, and arrested proliferating MDA-MB-231 cells at G1-phase. However, higher doses (50 µg/ml), triggered apoptosis in those cells. The low dose of ASPE also caused up-regulation of Cip1/p21 and Kip1/p27 and down-regulation of cyclins D1, D2, and E1 transcripts and their related cyclin dependent kinases: Cdk2, Cdk4, and Cdk6. The higher doses of ASPE initiated a dose-dependent apoptotic death in MDA-MB-231 by induction of Bax transcripts, inhibition of Bcl-2 and cleavage of Caspase-3 protein. Over-generation of reactive oxygen species (ROS) were also observed in MDA-MB-231 treated cells. CONCLUSIONS: These findings indicated that ASPE induces G1-phase arrest and apoptosis in MDA-MB-231 cells. ASPE may serve as a potential therapeutic agent for breast cancer.

Algal sulfated carrageenan inhibits proliferation of MDA-MB-231 cells via apoptosis regulatory genes.

Marine algae are prolific sources of sulfated polysaccharides, which may explain the low incidence of certain cancers in countries that traditionally consume marine food. Breast cancer is one of the most common types of non­skin cancer in females. In this study, extracted sulfated carrageenan (ESC), predominantly consisting of ι­carrageenan extracted from the red alga Laurencia papillosa, was characterized using Fourier transform infrared spectrometry. The biological effects of the identified extract were investigated and its potential cytotoxic activity was tested against the MDA­MB­231 cancer cell line. The biological biometer of the inhibitory concentration of the polysaccharide­treated MDA­MB­231 cells was determined as 50 µM. Treatment with 50 µM ESC inhibited cell proliferation and promptly induced cell death through nuclear condensation and DNA fragmentation. Characterization of polysaccharide­treated MDA­MB­231 cell death revealed that induction of apoptosis occurred via the activation of the extrinsic apoptotic caspase­8 gene. The apoptotic signaling pathway was regulated through caspase­3, caspase­9, p53, Bax and Bcl­2 genes. These findings suggest that ESC may serve as a potential therapeutic agent to target breast cancer via prompting apoptosis.