The Microalga Skeletonema marinoi Induces Apoptosis and DNA Damage in K562 Cell Line by Modulating NADPH Oxidase

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disease that activates multiple signaling pathways, causing cells to produce higher levels of reactive oxygen species (ROS). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are a major generator of ROS in leukemia, and marine natural products have shown promising activities for the treatment of hematopoietic malignancies. In the present study, we investigated the effect of the marine microalga Skeletonema marinoi (S.M.), a ubiquitous diatom that forms massive blooms in the oceans, on the human leukemia cell line K562. The effects of S.M. extract on cell viability, production of ROS, nitric oxide (NO), and apoptosis were examined. In this preliminary work, S.M. was able to decrease cell viability (p < 0.05) and increase apoptosis levels (p < 0.05) in K562 cells after 48 h of treatment. In addition, the levels of NOX, NO, and malondialdehyde (MDA) were reduced in K562-treated cells (p < 0.05), whereas the levels of SOD, CAT, and GPx increased during treatment (p < 0.05). Finally, analyzing Bax and Bcl-2 expression, we found a significant increase in the proapoptotic protein Bax and a sustained decrease in the antiapoptotic protein Bcl-2 (p < 0.05) in the K562-treated cells.

The Ocean’s Pharmacy: Health Discoveries in Marine Algae

“…Interestingly, anti-cancer activity featured the highest amount of microalgal studies (n = 7) compared to all the other bioactivities described in this review, which confirms it being a research hotspot [199]. In general, the tested macroalgal and microalgal extracts/compounds were successful in targeting one or multiple hallmarks of cancer-by displaying anti-proliferative effects (mainly through the induction of apoptosis) [72,[200][201][202][203][204][205][206][207][208][209][210][211][212][213][214], decreasing the inflammatory state [200,[211][212][213], migration capacity [215], angiogenesis potential [213], and adhesion properties [213]. When modulating oxidative stress, mechanisms to decrease cancerous cell survival differed between extracts or isolated compounds.…”

“…When modulating oxidative stress, mechanisms to decrease cancerous cell survival differed between extracts or isolated compounds. The methanol extract of Skeletonema marinoi [205] led to a decrease in NOx-generated ROS, increased antioxidant enzyme production, and decreased DNA damage in leukemia cells. On the other hand, the purified compounds triphlorethol-A [200] and fucoidan [210] increased oxidative stress by reducing antioxidant enzyme production, downregulating antioxidant pathways, and increasing DNA damage in brain glioma and oral cancer cells, respectively.…”