The Marine Dinoflagellate Alexandrium andersoni Induces Cell Death in Lung and Colorectal Tumor Cell Lines
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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.
KeywordsAlexandrium andersoni Marine bioactive dinoflagellate A549 HT29 TNF death signaling pathways SPE fractionation
The authors thank Mario Di Pinto, Massimo Perna, Flora Palumbo, and Mariano Amoroso for their technical support.
Conceived and designed the experiments: C.S. and C.G. C.S. and C.G. took part and contributed equally in the experiments with cell culture, real-time PCR, and western blotting. G. N. performed the chemical extractions. R.C. performed cell cycle analysis. Analyzed the data: A.I., A.F., R.C., C.S., and C.G. Contributed reagents/materials/analysis tools: AI. Wrote the paper: AI GR CS and C.G.
This study was supported by the Programma Operativo Nazionale 110_2093, National funding project and the European Marine Biological Research Infrastructure Cluster (EMBRIC), European funding project.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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