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

  • J Nat Prod. 2017 Feb 24;80(2):499-502. doi: 10.1021/acs.jnatprod.6b01051.
Takeo Tatsuta  1  2 ,  Masahiro Hosono  1  2 ,  Henki Rotinsulu  1  2 ,  Defny S Wewengkang  1  2 ,  Deiske A Sumilat  1  2 ,  Michio Namikoshi  1  2 ,  Hiroyuki Yamazaki  1  2
Affiliations
  • 1. 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.
  • 2. Faculty of Mathematic and Natural Sciences and ⊥Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
PMID: 28181805 DOI: 10.1021/acs.jnatprod.6b01051
Abstract

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.