The apoptosis-inducing activity towards leukemia and lymphoma cells in a cyanobacterial culture collection is not associated with mouse bioassay toxicity

Abstract

Cyanobacteria (83 strains and seven natural populations) were screened for content of apoptosis (cell death)-inducing activity towards neoplastic cells of the immune (jurkat acute T-cell lymphoma) and hematopoetic (acute myelogenic leukemia) lineage. Apoptogenic activity was frequent, even in strains cultured for decades, and was unrelated to whether the cyanobacteria had been collected from polar, temperate, or tropic environments. The activity was more abundant in the genera Anabaena and Microcystis compared to Nostoc, Phormidium, Planktothrix, and Pseudanabaena. Whereas the T-cell lymphoma apoptogens were frequent in organic extracts, the cell death-inducing activity towards leukemia cells resided mainly in aqueous extracts. The cyanobacteria were from a culture collection established for public health purposes to detect toxic cyanobacterial blooms, and 54 of them were tested for toxicity by the mouse bioassay. We found no correlation between the apoptogenic activity in the cyanobacterial isolates with their content of microcystin, nor with their ability to elicit a positive standard mouse bioassay. Several strains produced more than one apoptogen, differing in biophysical or biological activity. In fact, two strains contained microcystin in addition to one apoptogen specific for the AML cells, and one apoptogen specific for the T-cell lymphoma. This study shows the potential of cyanobacterial culture collections as libraries for bioactive compounds, since strains kept in cultures for decades produced apoptogens unrelated to the mouse bioassay detectable bloom-associated toxins.

Cyanobacteria as a Source for Novel Anti-Leukemic Compounds

“…Several studies have shown that cyanobacteria produce a great number of diverse apoptosis inducing compounds effective against leukemia cells [70,77,79,82,106]. The new unpublished results are in line with our previous findings [70,77,82] showing divergent and high amount of apoptotic activities (Fig.…”

“…A particular advantage with cell assays is that these are compatible with different types of samples, ranging from crude extracts to HPLC-fractions, or purified compounds. A selection of a few cell lines is often chosen to screen a whole culture collection [79][80][81][82] and selected extracts or purified compounds are scrutinized for anticancer effect on a large panel of cancer and normal cell lines [70,83] often combined with chemical analyses of extract to find the compound of interest [84].…”

Anticancer potential and cytotoxic effect of some freshwater cyanobacteria

“…Apoptosis leads to characteristic changes (morphology) and death of cells [26]. Cyanobacterial extracts have been found to contain long acting apoptotic compounds [10]. Research demonstrated that Oscillatoria terebriformis extract reduced cell viability of Human Lung Cancer Cell Lines by induction of apoptosis [27].…”

“…Similarly, cyanobacterium Cyanothece sp. had high anticancer effect on extracellular T-lymphoma cells [10].…”

Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria

“…These toxins do not distinguish between malignant and nonmalignant cells if microinjected into the cells [62]. Nevertheless, previous studies have shown that there is no correlation between phosphatase inhibitors and apoptogenic activity against SH-SY5Y-neuroblastoma and AML cells [58,63]. The lipopeptides hassallidin and puwainaphycin have been previously shown to have cytotoxic activity [64,65].…”