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.
Takeo TatsutaMasahiro HosonoHenki RotinsuluDefny S WewengkangDeiske A SumilatMichio NamikoshiHiroyuki YamazakiPublished in: Journal of natural products (2017)
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.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- induced apoptosis
- endothelial cells
- squamous cell carcinoma
- cystic fibrosis
- signaling pathway
- endoplasmic reticulum stress
- locally advanced
- induced pluripotent stem cells
- high fat diet induced
- oxidative stress
- amino acid
- papillary thyroid
- stem cells
- cell proliferation
- radiation therapy
- preterm birth
- risk assessment
- anti inflammatory
- bone marrow
- cell therapy