Estrogen receptor (ER)-positive
breast cancer is the main subtype of
breast cancer (BRCA) with high incidence and mortality.
Andrographolide (AD), a major active component derived from the
traditional Chinese medicine Andrographis paniculate, has substantial anti-
cancer effect in various
tumors. However, the antitumor efficacy and the underlying molecular mechanisms of AD on ER-positive
breast cancer are poorly understood. In the present study, we demonstrated that
andrographolide (AD) significantly inhibited the growth of ER-positive
breast cancer cells. Mechanistically, AD suppressed
estrogen receptor 1 (ESR1, encodes ER-α) transcription to inhibit
tumor growth. Further studies revealed that AD induced ROS production to down-regulate FOXM1-ER-α axis. Conversely, inhibiting ROS production with
N-acetylcysteine (NAC) elevated AD-decreased ER-α expression, which could be alleviated by FOXM1 knockdown. In addition, AD in combination with
fulvestrant (FUL) synergistically down-regulated ER-α expression to inhibit ER-positive
breast cancer both in vitro and in vivo. These findings collectively indicate that AD suppresses ESR1 transcription through ROS-FOXM1 axis to inhibit ER-positive
breast cancer growth and suggest that AD might be a potential therapeutic agent and
fulvestrant sensitizer for ER-positive
breast cancer treatment.