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
| Autor: | Adnan Ekhtiar, Mohammad Hawat, Hossam Murad, Ahmed Ghannam, Assef Abbas, Hussein Darwish, Abdulmunim Aljapawe, Oula Sbenati |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Red algae Cancer Research Cell cycle checkpoint Cell growth MDA-MB-231 Apoptosis Cell cycle Biology Molecular biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Biochemistry Cyclin-dependent kinase 030220 oncology & carcinogenesis Cancer cell Genetics biology.protein Viability assay Cyclin-dependent kinase 6 Primary Research G1-phase cell cycle arrest |
| Zdroj: | Cancer Cell International |
| ISSN: | 1475-2867 |
| DOI: | 10.1186/s12935-016-0315-4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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