Sensitization of human malignant lymphoid cells to etoposide by fucoidan, a brown seaweed polysaccharide.
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.


CONCLUSIONS
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.
Philchenkov
A
A
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine. a_philch@onconet.kiev.ua
Zavelevich
M
M
Imbs
T
T
Zvyagintseva
T
T
Zaporozhets
T
T
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage*; D005434:Flow Cytometry; D044645:Fucus / Q000737:chemistry; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D011134:Polysaccharides / Q000008:administration & dosage*; D012624:Seaweed / Q000737:chemistry*
D011134:Polysaccharides; D005047:Etoposide; C007789:fucoidan; D053148:Caspase 3