Marine Two-Headed Sphingolipid-Like Compound Rhizochalin Inhibits EGF-Induced Transformation of JB6 P⁺ Cl41 Cells

• Published in: Lipids Vol. 44; no. 9; pp. 777 - 785
• Main Authors: Fedorov, Sergey N, Makarieva, Tatyana N, Guzii, Alla G, Shubina, Larisa K, Kwak, Jong Y, Stonik, Valentin A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.09.2009; Springer-Verlag; Springer‐Verlag
• Subjects: Animals; Anticarcinogenic Agents - isolation & purification; Anticarcinogenic Agents - pharmacology; Anticarcinogenic properties; Apoptosis - drug effects; Biomedical and Life Sciences; Cell Line, Tumor; Cell Transformation, Neoplastic - drug effects; Fatty Alcohols - isolation & purification; Fatty Alcohols - pharmacology; Glycosides - isolation & purification; Glycosides - pharmacology; Humans; Leukemia - drug therapy; Life Sciences; Lipidology; Marine; Marine two‐headed sphingolipid‐like compound; Medical Biochemistry; Medicinal Chemistry; Mice; Microbial Genetics and Genomics; Neurochemistry; Nutrition; Original Article; p53‐dependent apoptosis; Porifera - chemistry; Rhizochalina; Tumor cells; Tumor Suppressor Protein p53 - metabolism; Marine two-headed sphingolipid-like compound; p53-dependent apoptosis; Tumor cells; Anticarcinogenic properties
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-009-3322-6

Rhizochalin [(2R,3R,26R,27R)-2,27-diamino-3-hydroxy-26-[(2R,3R,4S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy]octacosan-11-one], an antimicrobial and cytotoxic marine two-headed sphingolipid-like natural product, isolated from the sponge Rhizochalina incrustata, and some related compounds were studied as anticarcinogenic and proapoptotic agents. The corresponding effects were tested on the mouse skin epidermal JB6 P⁺ Cl 41 cell line, its stable transfectants, THP-1, HeLa, and SNU-C4 human tumor cells using a variety of assessments, including cell viability (MTS), flow cytometry, anchorage-independent soft agar, and luciferase assays. At 5-10 μM concentrations, rhizochalin was effective as an inhibitor of the malignant transformation of JB6 P⁺ Cl 41 cells or colony formation of human tumor cells, which exerted its action, at least in part, through the induction of p53-dependent apoptosis. Structure-activity relationship study showed aglycon of rhizochalin to be the most active while peracetylated aglycon was the least active among the compounds studied.