Coadministrating Luteolin Minimizes the Side Effects of the Aromatase Inhibitor Letrozole

Abstract

Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the K i values of luteolin and letrozole were estimated to be 2.44 mM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromataseexpressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs.

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women

“…Letrozole is a third-generation nonsteroid AI and can be effectively combined with the active center of aromatase to achieve an inhibitory effect greater than 99%. 9 Clinical studies have claimed that AIs are effective in treating endometrial hyperplasia and EC. 4,10 In 1 study, both the expression of estrogen receptor > and that of androgen receptor were shown to be significantly decreased in the anastrozole arm, which suggested that AIs may be an effective treatment.…”

Functional Investigation on Aromatase in Endometrial Hyperplasia in Polycystic Ovary Syndrome Cases

“…Letrozole is a third generation of non-steroid aromatase inhibitor, and it can effectively combine with the active center of aromatase with an inhibiting effect upon over 99% enzymes (Li et al, 2014). There have been clinical researches claiming that letrozole is effective in treating endometrial hyperplasia and endometrial carcinoma (Barker et al, 2009;Tabatabaie et al, 2013).…”

Impaired Fracture Healing in Sarco‐Osteoporotic Mice Can Be Rescued by Vibration Treatment Through Myostatin Suppression

“…The antigen‐antibody complexes were made visible by using syngene chemiluminescence detection system (GeneGnome). Immunoreactive bands ( n = 3) were quantitatively analyzed in triplicate by normalizing the band intensities against GAPDH on scanned films by ImageJ software …”