TY - JOUR
T1 - Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives
AU - Ohno, Osamu
AU - Morita, Maho
AU - Kitamura, Kazuhiro
AU - Teruya, Toshiaki
AU - Yoneda, Kozo
AU - Kita, Masaki
AU - Kigoshi, Hideo
AU - Suenaga, Kiyotake
N1 - Funding Information:
We thank Drs. K. Umezawa, K. Miyamoto, and S. Simizu, and Mr. Y. Niwa (Keio University), as well as Dr. D. Uemura (Kanagawa University) for their contributions to our studies. This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( 21221009 and 24310160 ), and by the MEXT -Supported Program for the Strategic Research Foundation at Private Universities, 2009–2013.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.
AB - Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.
KW - Actin
KW - Actin-depolymerizing activity
KW - Aplyronine A
KW - Apoptosis
KW - Mycalolide B
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U2 - 10.1016/j.bmcl.2012.12.052
DO - 10.1016/j.bmcl.2012.12.052
M3 - Article
C2 - 23357626
AN - SCOPUS:84873732831
VL - 23
SP - 1467
EP - 1471
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 5
ER -
