Tumor specific cytotoxicity of glucosylceramide.
To develop a new taxon of anti-cancer agent with lower side effect, this study described a tumor selective cytotoxicity of glucosylceramide extracted from malt feed of beer brewing waste. Interpretation of (13)C- and (1)H-NMR spectra identified the chemical structure of major component of glucosylceramide as 1-O-beta-D: -glucopyranosyl-2(2'-hydroxyeicosanoylamino)-4,11-octadecadiene-1,3-diol. Selective cytotoxicity was studied with three pairs of normal and cancer cells: liver, skin and lung. The glucosylceramide selectively lowered the relative viability of cancer cells. Of the pairs, the selectivity was most pronounced with the liver cells, and, for this reason, further experiment was conducted with this pair of normal (CS-HC) and cancer cells (HepG2) to get more insight into the selective toxicity. The glucosylceramide significantly increased the cell population at G(2)/M phase in HepG2 cells, and also increased the numbers of apoptotic (sub-G(0)/G(1)) cells, but to much lesser extent compared with the increase in G(2)/M phase. Treatment of HepG2 cells with this agent selectively disrupted the mitochondrial membrane integrity without activation of caspase pathway to induce apoptosis. These findings suggested that the glucosylceramide specifically suppressed the growth of cancer cells by inhibiting cell renewal capacity rather than induction of apoptosis. The underlying mechanism for the selectivity remains to be answered in the forthcoming study.
Oku
Hirosuke
H
Center of Molecular Biosciences, University of the Ryukyus, Nishihara, Okinawa, 903-0213, Japan. okuhiros@comb.u-ryukyu.ac.jp
Wongtangtintharn
Sawitree
S
Iwasaki
Hironori
H
Inafuku
Masashi
M
Shimatani
Masayuki
M
Toda
Takayoshi
T
D000821:Animal Feed; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001515:Beer; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002523:Edible Grain / Q000737:chemistry; D005963:Glucosylceramides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051336:Mitochondrial Membranes / Q000187:drug effects; D008517:Phytotherapy; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy
C524115:1-O-glucopyranosyl-2-(2'-hydroxyeicosanoylamino)-4,11-octadecadiene-1,3-diol; D000972:Antineoplastic Agents, Phytogenic; D005963:Glucosylceramides