Halenaquinone inhibits RANKL-induced osteoclastogenesis

Tsukamoto, Sachiko; Takeuchi, Tomoharu; Kawabata, Tomonori; Kato, Hikaru; Yamakuma, Michiko; Matsuo, Kanae; El‐Desoky, Ahmed H.; Losung, Fitje; Mangindaan, Remy E.P.; Voogd, Nicole J. de; Arata, Yoichiro; Yokosawa, Hideyoshi

doi:10.1016/j.bmcl.2014.09.043

Cited by 20 publications

(25 citation statements)

References 24 publications

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“…In addition, halenaquinone specifically inhibited the secondary DNA binding of RAD51, leading to the accumulation of chromosomal aberrations induced by unrepaired double-strand breaks [ 19 ]. Recently, Tsukamoto et al suggested that halenaquinone inhibited RANKL-induced osteoclastogenesis by suppressing the NFκB and Akt signaling pathways [ 20 ]. HQ, the marine natural product isolated from the Petrosia sponge, is a broad spectrum tyrosine kinase inhibitor and more potent than xestoquinone, with a carbonyl group at the C-3 position.…”

Section: Introductionmentioning

confidence: 99%

Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities

et al. 2015

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A marine polycyclic quinone-type metabolite, halenaquinone (HQ), was found to inhibit the proliferation of Molt 4, K562, MDA-MB-231 and DLD-1 cancer cell lines, with IC50 of 0.48, 0.18, 8.0 and 6.76 μg/mL, respectively. It exhibited the most potent activity against leukemia Molt 4 cells. Accumulating evidence showed that HQ may act as a potent protein kinase inhibitor in cancer therapy. To fully understand the mechanism of HQ, we further explored the precise molecular targets in leukemia Molt 4 cells. We found that the use of HQ increased apoptosis by 26.23%–70.27% and caused disruption of mitochondrial membrane potential (MMP) by 17.15%–53.25% in a dose-dependent manner, as demonstrated by Annexin-V/PI and JC-1 staining assays, respectively. Moreover, our findings indicated that the pretreatment of Molt 4 cells with N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger, diminished MMP disruption and apoptosis induced by HQ, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of HQ. The results of a cell-free system assay indicated that HQ could act as an HDAC and topoisomerase catalytic inhibitor through the inhibition of pan-HDAC and topoisomerase IIα expression, respectively. On the protein level, the expression of the anti-apoptotic proteins p-Akt, NFκB, HDAC and Bcl-2, as well as hexokinase II was inhibited by the use of HQ. On the other hand, the expression of the pro-apoptotic protein Bax, PARP cleavage, caspase activation and cytochrome c release were increased after HQ treatment. Taken together, our results suggested that the antileukemic effect of HQ is ROS-mediated mitochondrial apoptosis combined with the inhibitory effect on HDAC and topoisomerase activities.

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Section: Introductionmentioning

confidence: 99%

Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities

et al. 2015

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“…DNA-binding site within the RAD51-single-strand DNA filament complex. More recently, Tsukamoto et al [82] identified 65 as an inhibitor of the receptor activator of nuclear factor-κB ligand (RANKL)-induced upregulation of tartrate-resistant acid phosphatase (TRAP), which is involved in cell fusion, leading to the formation of multinucleated osteoclasts.…”

Section: Cyclostellettamines and Dehydrocyclostellettaminementioning

confidence: 99%

“…In addition, Takaku et al [81] demonstrated the inhibitory activity of the compound on DNA homologous pairing by direct binding to RAD51 enzyme, involved in the repair of DNA double-strand breaks, and subsequent likely competition with the double-strand DNA in the secondary DNA-binding site within the RAD51-single-strand DNA filament complex. More recently, Tsukamoto et al [82] identified 65 as an inhibitor of the receptor activator of nuclear factor-κB ligand (RANKL)-induced upregulation of tartrate-resistant acid phosphatase (TRAP), which is involved in cell fusion, leading to the formation of multinucleated osteoclasts.…”

Section: Cnidariamentioning

confidence: 99%

Histone Deacetylase Inhibitors from Marine Invertebrates

Luparello

Mauro

Arizza

et al. 2020

Biology

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Histone deacetylases (HDACs) are key components of the epigenetic machinery controlling gene expression. They are involved in chromatin remodeling events via post-translational histone modifications but may also act on nonhistone proteins, influencing many fundamental cellular processes. Due to the key involvement of HDACs in serious human pathologies, including cancer, HDAC inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of secondary metabolites showing active pharmacological properties and an extensive spectrum of biomedical applications. The aim of this review is to gather selected studies that report the extraction and identification of marine invertebrate-derived compounds that possess HDACi properties, grouping the producing species according to their taxonomic hierarchy. The molecular, biochemical, and/or physiological aspects, where available, and modes of action of these naturally occurring HDACis will be recapitulated, taking into consideration their possible utilization for the future design of analogs with increased bioavailability and efficacy, less toxicity, and, also, higher isoform selectivity.

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“…Xestosaprol C (56) was reported with cardiotonic activity (Nakamura et al, 1985). Halenaquinone (48), was found to be as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells (Tsukamoto et al, 2014).…”

Section: Othermentioning

confidence: 99%

Chemical and bioactive diversities of marine sponge Neopetrosia

Qaralleh

2016

Bangladesh J Pharmacol

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The marine sponge Neopetrosia contains about 27 species that is highly distributed in Indian Ocean, Atlantic Ocean (Caribbean Sea) and Pacific Ocean. It has proven to be valuable to the discovery of medicinal products due to the presence of various types of compounds with variable bio-activities. More than 85 compounds including alkaloids, quinones, sterols and terpenoids were isolated from this genus. Moreover, the crude extracts and the isolated compounds revealed activities such as antimicrobial, anti-fouling, anti-HIV, cytotoxic, anti-tumor, anti-oxidant, anti-protozoal, anti-inflammatory. Because only 9 out of 27 species of the genus Neopetrosia have been chemically studied thus far, there are signiﬁcant opportunities to ﬁnd out new chemical constituents from this genus.

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Halenaquinone inhibits RANKL-induced osteoclastogenesis

Cited by 20 publications

References 24 publications

Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities

Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities

Histone Deacetylase Inhibitors from Marine Invertebrates

Chemical and bioactive diversities of marine sponge <i>Neopetrosia</i>

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