The Marine Dinoflagellate Alexandrium andersoni Induces Cell Death in Lung and Colorectal Tumor Cell Lines

Mar Biotechnol (NY). 2018 Jun;20(3):343-352. doi: 10.1007/s10126-018-9817-5. Epub 2018 Apr 20.

Abstract

Dinoflagellates are one of the most important components in marine phytoplankton, second only to diatoms as primary producers. Dinoflagellates have also been reported to produce bioactive secondary metabolites such as polyethers and macrolides with potential applications as pharmaceuticals. Here, we tested the effect of the organic extract and its related enriched extracts from solid-phase extraction (SPE) of a strain of the dinoflagellate Alexandrium andersoni. We found that the SPE extracts induced high cytotoxicity towards two cancer cell lines (A549 lung cancer and HT29 colorectal cancer) without affecting normal cell viability. The SPE extracts activated two different cell death pathways in the two tumor cell lines at the gene expression level, with the involvement of the major mediators of the tumor necrosis factor (TNF) cell signaling cascade. In HT29 cells, in addition to TNF activation, a death signaling pathway in response to DNA damage was also induced. This is an interesting finding since the HT29 cell line is highly aggressive since it is p53 gene-defect and this DNA instability renders this type of cancer very resistant towards all chemotherapeutic agents. Another significant result is that two distinct chemical fractions were selectively able to induce different and specific responses on the two different tumor cells treated.

Keywords: A549; Alexandrium andersoni; HT29; Marine bioactive dinoflagellate; SPE fractionation; TNF death signaling pathways.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dinoflagellida / chemistry*
  • HT29 Cells
  • Humans
  • Signal Transduction / drug effects
  • Solid-Phase Synthesis Techniques

Substances

  • Antineoplastic Agents