Lycium barbarum inhibits growth of estrogen receptor positive human breast cancer cells by favorably altering estradiol metabolism.
Selective estrogen receptor modulators represent accepted therapy for estrogen receptor positive (ER+) breast cancer, exhibit adverse side effects, and reduce patient compliance. The use of phytoestrogen containing herbal medicines is limited because of efficacy and safety concerns. The ER+ MCF-7 model examined growth inhibitory effects of the medicinal herb Lycium barbarum (LB) and identified mechanistic leads for its efficacy. The MCF-7 cells maintained in 0.7% serum (17beta-estradiol, E2 < 1 nM) exhibited 11%-87% increased growth after treatment with 1nM to 20 nM E2. Growth promotion with 20 nM E2 exhibited 5.2-fold increased estrone (E1), 35.7% increased 2-hydroxyestrone (2-OHE1), 15.4% increased 16alpha-hydroxyestrone (16alpha-OHE1), and eightfold increased estriol (E3) formation. Treatment of E2 stimulated cells with LB exhibited a dose-dependent growth inhibition of 9.5%-42.8% at Day 3 and 33.9%-83.9% at Day 7. The 3-day inhibitory response to 1% LB (maximum cytostatic concentration) exhibited 84.8% increased E1, 3.6-fold increased 2-OHE1, 33.3% decreased 16alpha-OHE1, and 9.2-fold increased E3 formation. Thus, MCF-7 cells retain their mitogenic and metabolic response to E2 and LB downregulates E2-stimulated growth via the formation of antiproliferative 2-OHE1 and accelerated conversion of mitogenic 16alpha-OHE1 to antimitogenic E3.
Li
Go
G
Strang Cancer Prevention Center, New York, New York, USA.
Sepkovic
Daniel W
DW
Bradlow
H Leon
HL
Telang
Nitin T
NT
Wong
George Y C
GY
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D032305:Lycium; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis*
D010936:Plant Extracts; D011960:Receptors, Estrogen; D004958:Estradiol