alloin and Breast-Neoplasms

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.

Topics: Antigens, Neoplasm; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cyclin B; DNA Topoisomerases, Type II; DNA-Binding Proteins; Down-Regulation; Drug Resistance, Neoplasm; Emodin; Flow Cytometry; Gene Amplification; Humans; Mitosis; Receptor, ErbB-2

DNA ploidy and S phase fraction analysis by flow cytometry on breast and ovarian tumor cells continuously exposed to aloin, a natural anthraquinone, at two concentrations (20-60 microg/ml) was done. Untreated breast and ovarian tumor cells (control) showed an aneuploid pattern, with a mean DNA index of 2.10+/-0.10 and S phase fraction of 28.46+/-1.5 and 17.40+/-0.75%, respectively. Treatment of breast and ovarian tumor cells with aloin showed a persistent aneuploid pattern and a significantly dose-dependent increase in the percentage of S phase fraction and in the proportion of cells cycling at a higher ploidy level (>G2M). The polyploidization indicates that aloin does not inhibit initiation of DNA synthesis and that cells replicated a full complement of DNA but had difficulty in M phase.

Topics: Aloe; Breast Neoplasms; DNA; Emodin; Female; Humans; Ovarian Neoplasms; Ploidies; S Phase; Tumor Cells, Cultured