Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: topoisomerase IIalpha coamplification.
In the present study the cytotoxic activity of aloin, a natural anthracycline from Aloe plant, is reported against two human breast cancer cell lines; without (MCF-7) and with (SKBR-3) erbB-2-topoIIalpha coamplification. MCF-7cell line was shown to be more sensitive to aloin than SKBR-3 demonstrated by MTT and clonogenic assays, from which IC50 and 50% ICF values are reported to be 60 microg/ml, respectively, in the former cell line and as high as 150 and 80 microg/ml, respectively, in the latter, which are still far below the maximum tolerated dose of the compound. The effect of aloin is suggested to be brought about by more than one mechanism depending on the dose level and tumor phenotype. This was demonstrated by flow cytometric analysis, fluorescence microscopy and western blot analysis, which revealed that aloin at higher concentrations caused a reduction in the proportion of cells undergoing mitosis by induction of apoptosis, inhibition of topo II alpha protein expression and downregulation of cyclin B1 protein expression in MCF-7 cell line, whereas erbB-2 protein expression was not affected. Topo IIalpha protein expression was mildly downregulated in SKBR-3 cell line at higher concentrations only.
Esmat
Amr Y
AY
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. amyesmat@yahoo.com
Tomasetto
Catherine
C
Rio
Marie-Christine
MC
D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004642:Emodin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005434:Flow Cytometry; D005784:Gene Amplification; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D000951:Antigens, Neoplasm; D019926:Cyclin B; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004642:Emodin; D018719:Erb-b2 Receptor Tyrosine Kinases; C006457:alloin