Induction of apoptosis on human hepatocarcinoma cell lines by an alkyl resorcinol isolated from Lithraea molleoides.
OBJECTIVE
To study the mechanism of cytotoxicity of a new active 5-alkyl resorcinol [1, 3-dihydroxy-5- (tridec-4', 7'-dienyl) benzene] isolated from Lithraea molleoides leaves on liver tumor cells.


METHODS
Human hepatocarcinoma cell lines (HepG2 and Hep3B) in culture were treated with inhibitory concentrations, 50% of the compound, for 24 h. The induction of apoptosis was detected in treated cells by analysis of DNA fragmentation, DNA content, and acridine orange and propidium iodide staining.


RESULTS
After 24 h of 5-alkyl resorcinol treatment, both cell lines showed: (1) the typical morphological alterations of apoptosis; (2) DNA fragmentation, detected by laddering and appearance of a subG0 population by flow cytometry; and (3) condensed and fragmented nuclei by acridine orange-propidium iodide staining.


CONCLUSIONS
Based on the results, this compound exerts its cytotoxic effect in both hepatocellular cell lines through apoptotic cell death. For Hep3B, cells with mutated p53 and Fas, apoptosis would proceed by p53- or Fas-independent pathways.
Barbini
Luciana
L
Catedra de Virologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.
Lopez
Paula
P
Ruffa
Julieta
J
Martino
Virginia
V
Ferraro
Graciela
G
Campos
Rodolfo
R
Cavallaro
Lucia
L
D027926:Anacardiaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D003603:Cytotoxins / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009154:Mutation; D010936:Plant Extracts / Q000032:analysis / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D012118:Resorcinols / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C499259:1,3-dihydroxy-5-(tridec-4',7'-dienyl)benzene; D003603:Cytotoxins; D004273:DNA, Neoplasm; D053200:Fas-Associated Death Domain Protein; D010936:Plant Extracts; D012118:Resorcinols; D016159:Tumor Suppressor Protein p53