Breast cancer
Breast cancer is the most common cancer in women worldwide. In 2012, 1.7 million women were diagnosed with breast cancer and 522,000 women died from breast cancer.29 In 2010, 206,966 women and 2,039 men in the US were diagnosed with breast cancer, and 40,996 women and 439 men died from this disease.31 Current chemotherapy for advanced breast cancer often fails due to tumor resistance and adverse drug effects. Natural medicines have become an important complementary approach for breast cancer treatment.
Li et al32 first reported that LBPs inhibited the growth of Michigan Cancer Foundation-7 (MCF-7) cells by changing the metabolic pathways of estradiol. LBPs exhibited a dose-dependent growth inhibition of MCF-7 cells by 9.5%–42.8% at day 3 and by 33.9%–83.9% at day 7. The 3-day inhibitory response to 1% LBPs (maximum cytostatic concentration) exhibited 84.8% increase in estrone (E1), 3.6-fold increase in 2-OH-E1, 33.3% decrease in 16α-OH-E1, and 9.2-fold increase in estriol (E3) formation.32 Notably, LBPs appear to inhibit the proliferation of estrogen receptor-positive MCF-7 cells via modulation of estrogen metabolism and switch of metabolic pathways.
Shen and Du33 investigated the mechanisms for the anti-proliferative effects of LBPs on MCF-7 cells. These cells were treated with 10–300 mg/L LBPs for 24 hours. LBP treatment arrested MCF-7 cell cycle in S phase.33 LBPs dose-dependently activated extracellular signal-regulated kinase 1/2 (Erk1/2), which was associated with the expression of p53. These results indicated that LBPs inhibit the growth of MCF-7 cells through activation of Erk1/2.
Telang et al34 compared the efficacy of aqueous extracts from L. barbarum bark (LBB) and LBF on MCF-7 cells. LBB exhibited greater potency than LBF (95% reduction in the half maximal inhibitory concentration). LBB produced a 6.8-fold increase, 40% decrease, and a 3.7-fold increase in 2-OH-E1, 16α-OH-E1, and E3 formation. The corresponding values for LBF were 3.9, 33, and 10.5. LBB produced a 16.3-fold and twofold increase in 2-OH-E1:16α-OH-E1 and E3:16α-OH-E1 ratios, whereas LBF produced a six- and 2.9-fold increase, respectively. The efficacy of LBB is due to increased 2-OH-E1 formation, whereas that of LBF is due to accelerated conversion of 16α-OH-E1 to E3. Specific growth inhibitory profiles of LBB and LBF may be due to their distinct chemical composition and their complementary actions on estrogen metabolism.