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.

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Table 3 presents a pharmacological activity, an IC 50 , and a molecular mechanism of action for 36 marine natural products as reported in the peer-reviewed literature: astaxanthin ( 189 ) [182]; biselyngbyaside ( 190 ) [183]; Callyspongia sp. bisacetylenic alcohol ( 191 ) [184]; conicasterol E ( 192 ) [185]; 6”-debromohamacanthin A ( 193 ) [186]; dieckol ( 194 ) [187]; fructigenine A ( 195 ) [188]; geoditin A ( 196 ) [189]; gorgosterol ( 197 ) [190]; gracilioether B ( 198 ) [191]; gracilioether K ( 199 ) [192]; herdmanine K ( 200 ) [193]; hyrtioreticulin A ( 201 ) [194]; new Kunitz-type protease inhibitor InHVJ ( 202 ) [195]; jaspamide ( 203 ) [196]; latonduine A ( 204 ) [197]; leucettine L41 ( 205 ) [169]; manzamine A ( 206 ) [198]; nahuoic acid A ( 207 ) [199]; namalide ( 208 ) [200]; ningalins C and D ( 209 , 210 ) [201]; octaphlorethol A ( 114 ) [120]; petrosaspongiolide M ( 211 ) [202]; petrosiol A ( 212 ) [203]; phidianidine A ( 213 ) [204]; Poly-APS ( 214 ) [205]; Pseudoceratina sp.…”

Marine Cyanobacteria Compounds with Anticancer Properties: A Review on the Implication of Apoptosis

“…Apoptotic cells also develop nuclear alterations, visible as nuclear fragmentation and chromatin condensation [36]. Biselyngbyaside, a macrolide glycoside produced by Lyngbya sp., was found to induce apoptosis in mature osteoclasts, revealed by nuclear condensation [38]. Marine benthic Anabaena sp.…”

A Review Study on Macrolides Isolated from Cyanobacteria

“…Biselyngbyaside ( 17 ) inhibits RANKL-induced osteoclastogenesis by inhibiting the expression of c-Fos and NFATc1 in mouse monocytic RAW264 cells. Therefore, biselyngbyaside ( 17 ) is a potentially promising compound with therapeutic and preventive activities against bone-lytic diseases [52]. A toxic cyanobacterial macrolide, debromoaplysiatoxin ( 39 ), has been found to cause severe cutaneous inflammation in humans and other animals after topical application [25].…”