Cytotoxic, apoptotic and molecular effects of fucoidan as single agent and in combination with trastuzumab and docetaxel in HER2(+) breast cancer cells.
Bildiriler > Özet Bildiri
Yazarlar: Duygu Aygunes, Canfeza Sezgin, Ruchan Uslu, Buket KOSOVA
Journal of Clinical Oncology, , , Uluslararası, Özet Bildiri, Wos, cilt 33, ss e13520-e13520
DOI: 10.1200/jco.2015.33.15_suppl.e13520
Özet
e13520 Background: Breast cancer has high mortality rate in women. Drugs like docetaxel and trastuzumab are important in its treatment. However, in recent years supplements have gained importance in the treatment. Fucoidan, a sulfated polysaccharide mainly found in brown algae and seaweed, is a new candidate for therapy because of its anti-tumor activity. In our study, we aimed to determine cytotoxic, apoptotic and molecular effects of fucoidan and its synergistic and/or antagonistic effects in combination with docetaxel and trastuzumab in the HER2(+) breast cancer cell line MDA-MB-231. Methods: We set six groups for study including fucoidan, docetaxel, trastuzumab as single agents, fucoidan-docetaxel and fucoidan-trastuzumab combinations, untreated cells considered as negative control. IC50 value of each agent was obtained with the WST-1 cytotoxicity assay. Apoptosis was determined with the Annexin V, Active Caspase 2-3-8-9 and MitoCapture assays after applying the IC50value of each agent to MDA-MB-231 cell line. Gene expression levels were evaluated by real-time RT-PCR. MCF-10A non-cancerous epithelial breast cell line was used as a control cell line. Results: Both fucoidan-trastuzumab and fucoidan-docetaxel combinations showed higher cytotoxicity compared to untreated controls and the monodose groups of the agents in MDA-MB-231 cells. Besides, higher apoptotic levels were found for combinations. In contrast, no significant difference for cytotoxicity and apoptosis were found between fucoidan treated and untreated MCF-10A cells. At molecular level, APAF1, BAD, BAX, CASP2, CASP3, CASP8, CASP9, CD27, CDKN1, SFN, TGFb1, TP53, TP73, BRCA1, BRCA2, CDKN1C, CDKN2A, CTNNB1, MGMT, RB1, CCND1, JUN and MAPK1 genes changed significantly (p < 0.05) in fucoidan treated HER2 (+) breast ca cells when compared to untreated and monodose groups. Conclusions: As a result, fucoidan is an effective anti-tumor agent as single and in combination with docetaxel and trastuzumab in HER2(+) breast cancers cells. These findings suggest that fucoidan is a candidate natural product for breast cancer combination therapies, though this need to be validated in further studies.