Sensitization of human malignant lymphoid cells to etoposide by fucoidan, a brown seaweed polysaccharide
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A Philchenkov1, M Zavelevich, T Imbs
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine. a_philch@onconet.kiev.ua
Unlabelled:
The search for the substances sensitizing cancer cells to apoptosis induction by chemotherapeutic agents is a task of high importance in the modern strategy of anticancer therapy. THE AIM of the study was to investigate the apoptogenic and apoptosis-modulating activities of fucoidan (sulfated polysaccharide) isolated from far-eastern brown seaweeds Fucus evanescens in two human malignant lymphoid cell lines, MT-4 and Namalwa.
Methods:
Apoptosis was assessed morphologically and quantified by flow cytometry analysis of cells stained with propidium iodide. Caspase-3 activation was assayed by flow cytometry with the aid of labeled monoclonal antibodies.
Results:
The fucoidan at 500 microg/ml was not cytotoxic in MT-4 or Namalwa cells even in the setting of long-term presence in culture medium up to 14 days. Nevertheless, pretreatment of MT-4 but not Namalwa cells with fucoidan followed by the exposure to DNA topoisomerase II inhibitor etoposide led to about two-fold increase in the relative apoptotic index as compared with etoposide alone. Apoptosis enhancement of MT-4 cells by fucoidan was not accompanied by further increase in the number of the cells with active form of caspase-3.
Conclusion:
The present findings demonstrate for the first time that fucoidan enhances etoposide induced caspase-dependent cell death pathway in MT-4 but not Namalwa cell line. The mechanisms of such enhancement do not seem to be related directly to caspase-3 activation.
Insights
Fucoidan, a seaweed polysaccharide, enhances chemotherapy-induced apoptosis in certain cancer cells. This study found fucoidan sensitizes MT-4 lymphoid cells to etoposide, but not Namalwa cells, without directly increasing caspase-3 activation.
Area of Science:
- Marine Biotechnology
- Cancer Biology
- Pharmacology
Background:
- Identifying agents that sensitize cancer cells to chemotherapy is crucial for effective anticancer therapy.
- Fucoidan, a sulfated polysaccharide from brown seaweed, is being investigated for its biological activities.
Purpose of the Study:
- To investigate the apoptogenic and apoptosis-modulating activities of fucoidan.
- To assess fucoidan's effects on two human malignant lymphoid cell lines (MT-4 and Namalwa) in combination with chemotherapeutic agents.
Main Methods:
- Morphological assessment and flow cytometry were used to quantify apoptosis.
- Caspase-3 activation was measured using flow cytometry with labeled monoclonal antibodies.
Main Results:
- Fucoidan (500 microg/ml) was not cytotoxic to MT-4 or Namalwa cells.
- Pretreatment with fucoidan significantly increased etoposide-induced apoptosis in MT-4 cells by approximately two-fold compared to etoposide alone.
- This apoptosis enhancement in MT-4 cells was not associated with increased active caspase-3 levels.
Conclusions:
- Fucoidan enhances etoposide-induced, caspase-dependent cell death in the MT-4 cell line, but not in the Namalwa cell line.
- The mechanism of fucoidan's apoptosis enhancement in MT-4 cells does not appear to be directly linked to caspase-3 activation.