4.6 Article

Cytotoxic activity of fucoxanthin, alone and in combination with the cancer drugs imatinib and doxorubicin, in CML cell lines

Journal

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 59, Issue -, Pages 24-33

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2018.02.006

Keywords

Antiproliferation; CML; Doxorubicin; Fucoxanthin; Imatinib

Funding

  1. Research Line NOVELMAR - Novel marine products with biotechnological applications, integrated into the Structured Program of RDI INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources - Northern Regional Operation [NORTE-01-0145-FEDER-000035]
  2. ERDF, through the Competitiveness and Trade Expansion Program (COMPETE)
  3. Foundation for Science and Technology (FCT) [UID/Multi/04423/2013]
  4. Institute of Biomedical Sciences Abel Salazar, University of Porto
  5. [NOVELMAR/IA3/2016-041]

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In the present study, we evaluate the in vitro cytotoxicity of fucoxanthin (Fx) on two human leukemia cell lines, K562 and TK6, alone and in combination with the conventional anticancer drugs imatinib (Imat) and doxorubicin (Dox). For the purpose, we assessed the cytotoxic and proliferation effects by cell count, induction of DNA damage by comet assay, and cell death by nuclear condensation, annexin V staining, coupled with propidium iodide uptake, and protein expression of Bax, caspase-3, and Bcl-2 (western blot). Our results show that Imat increased cytotoxicity in TK6 cells and inhibited proliferation in K562 cells, while Dox decreased cell viability and proliferation in both cell lines. Fx per se increased cytotoxicity against K562 cells and decreased cell proliferation of K562 and TK6 cells. The effects were confirmed by phase contrast microscopy. However, the antiproliferative effects are not explained by induction of DNA damage or cell death. In co-incubation, Fx increased antiproliferative effects of both drugs in the cell lines tested, however no differences where observed relative to Fx alone. This study unveiled in vitro cytotoxicity of Fx by inhibition of cell proliferation in both cell lines. Further studies are needed to elucidate the signal transduction pathways and molecular targets involved in that effect.

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