Identification of a molecular target of kurahyne, an apoptosis-inducing lipopeptide from marine cyanobacterial assemblages

Arihiro Iwasaki; Osamu Ohno; Shun Katsuyama; Maho Morita; Yukiko Sasazawa; Shingo Dan; Siro Simizu; Takao Yamori; Kiyotake Suenaga

doi:10.1016/j.bmcl.2015.09.044

Identification of a molecular target of kurahyne, an apoptosis-inducing lipopeptide from marine cyanobacterial assemblages

Bioorg Med Chem Lett. 2015 Nov 15;25(22):5295-8. doi: 10.1016/j.bmcl.2015.09.044. Epub 2015 Sep 21.

Authors

Arihiro Iwasaki¹, Osamu Ohno², Shun Katsuyama³, Maho Morita⁴, Yukiko Sasazawa³, Shingo Dan⁵, Siro Simizu³, Takao Yamori⁵, Kiyotake Suenaga⁶

Affiliations

¹ Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama, Kanagawa 223-8522, Japan.
² School of Advanced Engineering, Kogakuin University, 2665-1 Nakanocho, Hachioji, Tokyo 192-0015, Japan.
³ Department of Applied Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama, Kanagawa 223-8522, Japan.
⁴ Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
⁵ Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
⁶ Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama, Kanagawa 223-8522, Japan. Electronic address: suenaga@chem.keio.ac.jp.

PMID: 26428873
DOI: 10.1016/j.bmcl.2015.09.044

Abstract

In 2014, we isolated kurahyne, an acetylene-containing lipopeptide, from a marine cyanobacterial assemblage of Lyngbya sp. Kurahyne exhibited growth-inhibitory activity against human cancer cells, and induced apoptosis in HeLa cells. However, its mode of action is not yet clear. To elucidate its mode of action, we carried out several cell-based assays, and identified the intracellular target molecule of kurahyne as sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA). In addition, we found that kurahyne inhibited the differentiation of macrophages into osteoclasts.

Keywords: Apoptosis; ER stress; Kurahyne; Marine natural product; SERCA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Affinity Labels / chemistry
Alkynes / chemistry
Alkynes / pharmacology*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis
Calcium / metabolism
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress / drug effects
HeLa Cells
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism
Humans
Lipopeptides / chemistry
Lipopeptides / pharmacology*
Macrophages / cytology
Macrophages / drug effects
Oscillatoria / chemistry*
Osteoclasts / cytology
Osteoclasts / drug effects
Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors*
Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
Transcription Factor CHOP / genetics
Transcription Factor CHOP / metabolism
Transcriptional Activation

Substances

Affinity Labels
Alkynes
Antineoplastic Agents
DDIT3 protein, human
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Lipopeptides
Transcription Factor CHOP
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Calcium