title: Effect of curcumin on irradiated and estrogen-transformed human breast             cell lines.
abstract: Curcumin (diferuloyl methane) is a well known antioxidant that exerts antiproliferative and apoptotic effects. Curcumin effect was evaluated in a breast cancer model that was developed using the immortalized breast epithelial cell line MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17β-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) MCF-10F; ii) Estrogen cell line; iii) a malignant Alpha3 cell line; iv) a malignant and tumorigenic, Alpha5 cell line; and v) a cell line derived from Alpha5 injected into the nude mice that gave rise to Tumor2 cell line. Curcumin decreased anchorage-independent growh in transformed breast cancer cell lines in comparison to their counterparts and increased the percentage of cells from G₀/G₁ with a concomitant increase in G₂/M phases, as well as a decrease in PCNA and Rho-A protein expression. Among the oncogenes, c-Ha-Ras and Ras homologous A (Rho-A) are important cell signaling factors for malignant transformation and to reach their active GTP bound state, Ras proteins must first release bound GDP mediated by a guanine nucleotide releasing factor (GRF). Then curcumin decrease RasGRF1 protein expression in malignant cell lines. Further, differential expression levels of cleaved (ADP) ribose polymerase 1 (PARP-1) and phosphorylated histone H2AX (γ-H2AX) were observed after curcumin treatment. It seems that PARP-1 similar to H2AX, confers cellular protection against radiation and estrogen-induced DNA damage mediated by curcumin. Therefore, targeting either PARP-1 or H2AX may provide an effective way of maximizing the therapeutic value of antioxidants for cancer prevention.
authors: Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile. gmc24@columbia.edu
authors: Gloria M
authors: GM
authors: Calaf
authors: Carlos
authors: C
authors: Echiburú-Chau
authors: Gengyun
authors: G
authors: Wen
authors: Adayabalam S
authors: AS
authors: Balajee
authors: Debasish
authors: D
authors: Roy
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001940:Breast / Q000166:cytology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D003474:Curcumin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000528:radiation effects; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020666:ras-GRF1 / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D004967:Estrogens; C513039:RASGRF1 protein, human; D020666:ras-GRF1; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D003474:Curcumin