PMID- 21160418
OWN - NLM
STAT- MEDLINE
DCOM- 20110823
LR  - 20151119
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 22
IP  - 3
DP  - 2011 Mar
TI  - Additive effects of trastuzumab and genistein on human breast cancer cells.
PG  - 253-61
LID - 10.1097/CAD.0b013e3283427bb5 [doi]
AB  - Soy isoflavone genistein, a tyrosine kinase inhibitor and agonist of estrogen 
      receptor-beta (ERbeta), is known to have antitumoral properties. Given that ERbeta often 
      is coexpressed with HER2 in breast cancer, both functions of genistein might be 
      able to enhance the antitumoral action of trastuzumab. In this in-vitro study, we 
      tested whether combined treatment with genistein and trastuzumab exerts additive 
      effects on breast cancer cells. HER2-overexpressing breast cancer cell lines were 
      treated with genistein alone and in combination with trastuzumab. The effects of 
      this treatment on proliferation and gene expression were analyzed. Treatment with 
      high-dose genistein (10 mumol/l) significantly increased the growth-inhibitory 
      effect of trastuzumab on HER2-overexpressing, ERalpha/beta-positive BT-474 breast cancer 
      cells. Combinatory treatment using lower doses of trastuzumab exerted similar 
      effects as a single treatment with standard doses of this drug. In contrast, this 
      effect was absent in ERalpha-negative SK-BR-3 cells. Similar results were obtained 
      after cotreatment with the ERbeta agonist, 2,3-bis(4-hydroxyphenyl)propionitrile. 
      The growth-inhibitory effect of both drugs was accompanied by an increased 
      expression of the putative tumor suppressor ERbeta variant, cx, and their 
      combination further elevated mRNA levels of this receptor. In conclusion, 
      genistein significantly enhanced the antitumoral effect of trastuzumab on BT-474 
      breast cancer cells in vitro. The relevance of these data particularly for women 
      with HER2-overexpressing and ERalpha/beta-positive breast cancer has to be verified in 
      animal or clinical studies.
FAU - Lattrich, Claus
AU  - Lattrich C
AD  - Department of Obstetrics and Gynecology, University Medical Center Regensburg, 
      Regensburg, Germany.
FAU - Lubig, Julia
AU  - Lubig J
FAU - Springwald, Anette
AU  - Springwald A
FAU - Goerse, Regina
AU  - Goerse R
FAU - Ortmann, Olaf
AU  - Ortmann O
FAU - Treeck, Oliver
AU  - Treeck O
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Protein Kinase Inhibitors)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Synergism
MH  - Estrogen Receptor alpha/genetics
MH  - Estrogen Receptor beta/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genes, erbB-2
MH  - Genistein/*pharmacology
MH  - Humans
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Receptor, ErbB-2/genetics
MH  - Trastuzumab
EDAT- 2010/12/17 06:00
MHDA- 2011/08/24 06:00
CRDT- 2010/12/17 06:00
PHST- 2010/12/17 06:00 [entrez]
PHST- 2010/12/17 06:00 [pubmed]
PHST- 2011/08/24 06:00 [medline]
AID - 10.1097/CAD.0b013e3283427bb5 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2011 Mar;22(3):253-61. doi: 10.1097/CAD.0b013e3283427bb5.