Planta Med 2007; 73(2): 173-175
DOI: 10.1055/s-2006-957069
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Bone Resorption in Cultures of Mouse Calvariae by Apicularen A

JangJa Hong1 , 2 , 3 , Hirokazu Sasaki1 , Kazuaki Niikura4 , Maiko Yanai1 , Yasuhiro Nakano1 , Aya Yokomakura1 , Kenji Ishihara1 , Noriyasu Hirasawa1 , Young-Sook Kang3 , Joa Sub Oh2 , Jong Hwan Kwak2 , OkPyo Zee2 , Kazuo Ohuchi1 , 5
  • 1Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan
  • 2Laboratory of Pharmacognosy, Graduate School of Pharmacy, Sungkyunkwan University, Suwon, Kyungi-do, Korea
  • 3Laboratory of Pathophysiology, College of Pharmacy, Sookmyung Women’s University, Seoul, Korea
  • 4Pharmacology Research Laboratories, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan
  • 5Faculty of Pharmacy, Yasuda Women’s University, Hiroshima, Japan
Further Information

Publication History

Received: February 9, 2006

Accepted: November 13, 2006

Publication Date:
18 December 2006 (online)

Abstract

Apicularens A and B were isolated from the myxobacterial genus Chondromyces apiculatus JW184. Apicularen A inhibited bafilomycin A1-sensitive ATP-dependent proton transport into microsome vesicles more potently than apicularen B. Bone resorption in cultures of mouse calvariae induced by human parathyroid hormone (PTH) or interleukin-1β (IL-1β) was inhibited by apicularen A at 10 and 100 nM, while apicularen B had no effect. The bisphosphonate incadronate inhibited bone resorption at 100 nM, being less effective than apicularen A. Our findings indicate that apicularen A inhibits bone resorption induced by PTH or IL-1β more potently than apicularen B, probably due to inhibition of the V-ATPase.

References

  • 1 Kunze B, Jansen R, Sasse F, Höfle G, Reichenbach H. Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): production, physico-chemical and biological properties.  J Antibiot. 1998;  51 1075-80
  • 2 Bhattacharjee A, Sequil O R, De Brabander J K. Total synthesis and biological evaluation of apicularen A and synthetic analogs.  Tetrahedron Lett. 2001;  42 1217-20.
  • 3 Huss M, Sasse F, Kunze B, Jansen R, Steinmetz H, Ingenhorst G. et al . Archazolid and apicularen: novel specific V-ATPase inhibitors.  BMC Biochem. 2005;  6 13-22
  • 4 Blair H C, Teitelbaum S L, Ghiselli R, Gluck S. Osteoclastic bone resorption by a polarized vacuolar proton pump.  Science. 1989;  245 855-7
  • 5 Sundquist K, Lakkakorpi P, Wallmark B, Väänänen K. Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption.  Biochem Biophys Res Commun. 1990;  168 309-13
  • 6 Hong J, Ishihara K, Zee O, Ohuchi K. Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line HL-60.  Planta Med. 2005;  71 306-12
  • 7 Hong J, Yokomakura A, Nakano Y, Ban H S, Ishihara K, Ahn J W. et al . Induction of nitric oxide production by the cytostatic macrolide apicularen A [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14-dihydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1-propenyl], (2Z,4Z)-(9CI)] and possible role of nitric oxide in apicularen A-induced apoptosis in RAW 264.7 cells.  J Pharmacol Exp Ther. 2005;  312 968-77
  • 8 Niikura K, Takeshita N, Takano M. A vacuolar ATPase inhibitor, FR167356, prevents bone resorption in ovariectomized rats with high potency and specificity: potential for clinical application.  J Bone Miner Res. 2005;  20 1579-88
  • 9 Hong J, Yamaki K, Ishihara K, Ahn J W, Zee O, Ohuchi K. Induction of apoptosis RAW 264.7 cells by the cytostatic macrolide apicularen A.  J Pharm Pharmacol. 2003;  55 1299-306

Prof. Dr. Kazuo Ohuchi

Laboratory of Pathophysiological Biochemistry

Graduate School of Pharmaceutical Sciences

Tohoku University

6-3 Aoba Aramaki

Aoba-ku

Sendai

Miyagi 980-8578

Japan

Phone: +81-22-795-6862

Fax: +81-22-795-6863

Email: ohuchi-k@mail.pharm.tohoku.ac.jp

    >