Caspase-3 status is a determinant of the differential responses to genistein between MDA-MB-231 and MCF-7 breast cancer cells.
Genistein, a soy isoflavone with anti-tumor properties, has both estrogenic and non-estrogenic activities. Genistein sensitive/estrogen receptor negative (ER-) MDA-MB-231 cells and genistein resistant/ER+MCF-7 cells are frequently cited as examples of differential responses to genistein due to different ER status. Other factors that may affect genistein response, however, are largely unknown. Based on our finding that MCF-7 is caspase-3 deficient, we examined whether caspase-3 status plays a role in the differential responses between the two cell lines. We demonstrate that reconstitution of caspase-3 significantly sensitizes MCF-7 cells to genistein. Specific knockdown of caspase-3 in MDA-MB-231 cells renders the cells resistant to genistein. We also found that caspases-4 and -10 were downregulated in MCF-7 cells. Reconstitution of caspase-10 in MCF-7 cells, however, resulted in little sensitization. Moreover, we show that caspase-3 downregulation is very common in breast cancer cell lines and tumor tissues. Taken together, our data indicate that caspase-3 is a critical determinant of cellular response to genistein, which may have important implications in studying soy/genistein-mediated anti-tumor activities.
Yang
Shihe
S
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Zhou
Qiong
Q
Yang
Xiaohe
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D053455:Caspase 10 / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis* / Q000172:deficiency; D053471:Caspases, Initiator / Q000096:biosynthesis; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011960:Receptors, Estrogen / Q000172:deficiency / Q000378:metabolism
D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D019833:Genistein; C093516:CASP4 protein, human; D053455:Caspase 10; D053148:Caspase 3; D053471:Caspases, Initiator