Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by down-regulating nicotinic acetylcholine receptors.
Large-scale epidemiological cohort studies performed in the United States indicate that breast cancer risk is associated with active and passive smoking. As of yet, however, there is no direct evidence of antitumor effects by agents that block the effect of tobacco compound nicotine (Nic) on relevant nicotinic receptors (nAChR) involved in breast tumorigenesis. In the present study, the expression profiles of different nAChR subunits in the human breast cancer cell line (MDA-MB-231) were characterized by RT-PCR. Nic (>0.1 microM, 6 h) significantly increased alpha9-nAChR mRNA and protein expression levels in human breast cancer cells (MDA-MB-231 cells). On the other hand, combined treatment with luteolin (Lut, 0.5 microM) and quercetin (Que, 0.5 microM) profoundly decreased MDA-MB-231 proliferation by down-regulating alpha9-nAChR expression. MDA-MB-231 cells were cultured in soft agar to evaluate anchorage-independent colony formation; combined treatment of Lut+Que inhibited Nic-induced MDA-MB-231 colony formation. Interestingly, the number of colonies formed was profoundly reduced in alpha9-nAChR knockdown (Si alpha9) cells in the combined (Lut+Que)-treated group as compared to the relevant control groups. Such results show that Lut- or Que-induced antitransforming activities were not limited to specific inhibition of the alpha9-nAChR receptor. Both alpha5- and alpha9-nAChR appear to be important molecular targets for Lut- and Que-induced antitumor effects in human breast cancer cells.
Shih
Yung-Leun
YL
Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Liu
Hui-Ching
HC
Chen
Ching-Shyang
CS
Hsu
Chung-Huei
CH
Pan
Min-Hsiung
MH
Chang
Hui-Wen
HW
Chang
Chien-Hsi
CH
Chen
Feng-Chia
FC
Ho
Chi-Tang
CT
Yang
Yi-Yuan
YY
Ho
Yuan-Soon
YS
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism
D020033:Protein Isoforms; D011978:Receptors, Nicotinic; D009538:Nicotine; D011794:Quercetin; D047311:Luteolin