Growth factors and chemotherapeutic modulation of breast cancer cells.
A variety of molecules including growth factors are involved in the metastasis of breast cancer cells to bone. We have investigated the effects of osteoblast derived growth factors, such as insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-beta1), on doxorubicin (adriamycin)-induced apoptosis and growth arrest of estrogen receptor positive (ER+) (MCF-7) and negative (ER-) (MDA-MB-435) breast cancer cell lines. Human breast normal epithelial (MCF-10A), breast cancer (MCF-7) and metastatic breast cancer (MDA-MB-435) cell lines were exposed to different doses of doxorubicin (0.1, 1 or 10 microM) at various exposure times (12, 24 or 48 h). The doxorubicin cytotoxicity was found to be higher in cancer cell lines (MDA-MB-435 and MCF-7) compared with normal breast epithelial cells (MCF-10A cells). Doxorubicin appeared to exert a blockade of MCF-7 and MDA-MB-435 cells at the G2/M phase, and induced apoptosis in MDA-MB-435 (29 +/- 4.2% vs 3.4 +/- 1.9% control) as assessed by flow cytometry, DNA fragmentation and terminal deoxynucleotidyl-transferase mediated deoxyuridine 5-triphosphate and biotin nick-end labelling (TUNEL) assays. Estradiol (E2) stimulated the growth of MCF-7 cells and increased the distribution of the cells at the G2/M and S phases. Exogenous IGF-1 partially neutralized the doxorubicin cytotoxicity in both cancer cell lines (MCF-7 and MDA-MB-435). Similarly, TGF-beta1 partially neutralized the doxorubicin cytotoxicity in MDA-MB-435 cells by reducing the number of cells at the <G1 phase (from 29% to 6.4%) and enhanced the doxorubicin blockade of MCF-7 (E2-) at the G0/G1 phase. Results showed that the osteoblast-derived growth factors could affect the chemotherapy response of breast cancer cells, thereby allowing for the possibility of chemotherapeutic modulation.
Ciftci
Kadriye
K
Temple University, School of Pharmacy, Department of Pharmaceutical Sciences, 3307 N. Broad Street, Philadelphia, PA 19140, USA. kadriye.ciftci@temple.edu
Su
Jiangfeng
J
Trovitch
Peter B
PB
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000187:drug effects*; D010006:Osteoblasts / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000187:drug effects*; D053773:Transforming Growth Factor beta1
D000970:Antineoplastic Agents; D006133:Growth Substances; D011960:Receptors, Estrogen; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin