Biselyngbyaside, isolated from marine cyanobacteria, inhibits osteoclastogenesis and induces apoptosis in mature osteoclasts
ABSTRACT The mass and function of bones depend on the maintenance of a complicated balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An inhibitor of osteoclast differentiation and/or function is expected to be useful for treatment of bone lytic diseases such as osteoporosis, rheumatoid arthritis, and tumor metastasis into bone. Biselyngbyaside is a recently isolated macrolide compound from marine cyanobacteria Lyngbya sp. that shows wide-spectrum cytotoxicity toward human tumor cell lines. In this study, we investigated the effects of biselyngbyaside on osteoclast differentiation and function. Biselyngbyaside inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in mouse monocytic RAW264 cells and primary bone marrow-derived macrophages at a low concentration. Similarly, biselyngbyaside suppressed osteoblastic cell-mediated osteoclast differentiation in cocultures. In the RANKL-induced signaling pathway, biselyngbyaside inhibited the expression of c-Fos and NFATc1, which are important transcription factors in osteoclast differentiation. In mature osteoclasts, biselyngbyaside decreased resorption-pit formation. Biselyngbyaside also induced apoptosis accompanied by the induction of caspase-3 activation and nuclear condensation, and these effects were negated by the pancaspase inhibitor z-VAD-FMK. Taken together, the present findings indicate that biselyngbyaside suppresses bone resorption via inhibition of osteoclastogenesis and induction of apoptosis. Thus, biselyngbyaside may be useful for the prevention of bone lytic diseases.
SourceAvailable from: Maria Helena Fernandes[Show abstract] [Hide abstract]
ABSTRACT: Marine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been the most explored and, besides cytotoxicity in tumor cell lines, several compounds have emerged as templates for the development of new anticancer drugs. The mechanisms implicated in the cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still largely overlooked but several studies point to an implication in apoptosis. This association has been related to several apoptotic indicators such as cell cycle arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase cascade, alterations in specific proteins levels and alterations in the membrane sodium dynamics. In the present paper a compilation of the described marine cyanobacterial compounds with potential anticancer properties is presented and a review on the implication of apoptosis as the mechanism of cell death is discussed.Marine Drugs 10/2012; 10(10):2181-207. DOI:10.3390/md10102181 · 3.51 Impact Factor
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ABSTRACT: Cyanobacteria are among the earliest of inhabitant s of Planet Earth and are highly diverse members of the current global biodiversity and are making significant cont ributions to the Carbon and Nitrogen bio-geochemica l cycles, particularly in the deep oceans. Cyanobacteria in recent year have gained importance because of their potential use in various areas of research. This diverse group has application in var ious fields like biotechnology, pharmacology, agric ulture etc. Due to presence of wide spectrum of bioactive compounds cy anobacteria has possesses antiviral, antibacterial, antifungal and anticancer activities. Several strains of cyanobact eria are also rich in food supplements. Further nit rogen fixing capacity of cyanobacteria has attracted agriculturists and rese archers and they used blue green algae as a compone nt of biofertilizers to improve both the fertility of soil as well as growt h of plants. Recent studies have also shown that cy anobacteria have capability to degrade environmental pollutants and are also being used as a promising source of altern ative energy. In spite of all these investigation and research more effort s should be made in search of more strains of cyano bacteria and genetically modifying known strains to ensure maxim um production of the desired products.
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ABSTRACT: Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Aging induces bone loss due to decreased osteoblastic bone formation and increased osteoclastic bone resorption. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. It is undoubted that pharmacological and nutritional factors are involved in the prevention of age-related bone loss. In the search for the appropriate treatment of osteoporosis, there is an interesting area of marine organisms and phytopharmacology. Extracts of marine algae and other marine derived compounds have a favorable effect on bone metabolism. This review discusses the current pharmacological therapies for osteoporosis and bioactive natural products from marine for the anti-osteoporotic research.01/2014; DOI:10.1016/j.bionut.2013.12.005