Lissoclibadin 1, a Polysulfur Aromatic Alkaloid from the Indonesian Ascidian Lissoclinum cf. badium, Induces Caspase-Dependent Apoptosis in Human Colon Cancer Cells and Suppresses Tumor Growth in Nude Mice.
Lissoclibadins, polysulfur aromatic alkaloids, were isolated from the Indonesian ascidian Lissoclinum cf. badium. Lissoclibadins 1 (1), 3 (2), 4 (3), 7 (4), 8 (5), and 14 (6) inhibited the growth of four human solid cancer cell lines: HCT-15 (colon adenocarcinoma), HeLa-S3 (cervix adenocarcinoma), MCF-7 (breast adenocarcinoma), and NCI-H28 (mesothelioma). Lissoclibadin 1 (1) exerted the most potent cytotoxic effects in vitro and mainly promoted apoptosis through an intrinsic pathway with the activation of a caspase-dependent pathway in HCT-15 cells. In vivo studies demonstrated that 1 suppressed tumor growth in nude mice carrying HCT-15 cells without significant secondary adverse effects. In conclusion, the results obtained in the present study demonstrate that 1 has potential as a chemotherapeutic candidate for preclinical investigations.
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Takeo
T
Tatsuta
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Masahiro
M
Hosono
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Henki
H
Rotinsulu
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Defny S
DS
Wewengkang
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Deiske A
DA
Sumilat
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Michio
M
Namikoshi
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences and ‡Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558, Japan.|Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
Hiroyuki
0000-0002-1540-7255
H
Yamazaki
D000230:Adenocarcinoma; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007214:Indonesia; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D014561:Urochordata / Q000737:chemistry*
D000470:Alkaloids; D000970:Antineoplastic Agents; C000621082:lissoclibadin 1; D020169:Caspases