Andrographolide Inhibits ER-Positive Breast Cancer Growth and Enhances Fulvestrant Efficacy via ROS-FOXM1-ER-α Axis

Abstract

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.

Andrographolide Synergized with Doxorubicin to Induce Cell Death in Breast Cancer Cell via ROS-dependent DNA Damage

“…In fact, our results are similar to some earlier reports [20,37,38,[43][44][45][46] . For instance, andrographolide sensitizes estrogen receptor (ER)-positive breast cancer to fulvestrant treatment by increasing cellular ROS levels [43] .…”

“…In fact, our results are similar to some earlier reports [20,37,38,[43][44][45][46] . For instance, andrographolide sensitizes estrogen receptor (ER)-positive breast cancer to fulvestrant treatment by increasing cellular ROS levels [43] . Taken together, our ndings might have clinical indications, and andrographolide available clinically may be an ideal sensitizer to increase the e cacy of doxorubicin in the treatment of breast cancer.…”

The therapeutic effect of traditional Chinese medicine on breast cancer through modulation of the Wnt/β-catenin signaling pathway

“…Wall. ex Nees (Acanthaceae; Andrographis herba) ( Xu et al, 2022 ), Scleromitrion diffusum (Willd.) R. J. Wang (Rubiaceae; Hedyotis diffusa willd) ( Li et al, 2017 ), Bupleurum chinense DC.…”

“…This heterogeneity manifests in the form of multiple breast cancer subtypes. Clinically, two predominant subtypes emerge based on receptor status: the ER-positive, PR-positive, HER-2 amplification type, and the Triple-Negative Breast Cancer (TNBC) ( Xu et al, 2022 ). Delving deeper into molecular markers, breast cancer can be categorized into Luminal A type, Luminal B type, HER-2 overexpression type, and Triple-Negative type, determined by the expression levels of ER, PR, HER-2, and Ki-67 ( Gangrade et al, 2018 ; Fumagalli and Barberis, 2021 ; Liu H. Y. et al, 2022 ).…”

“…Wall. ex Nees (Acanthaceae; Andrographis herba), in nude mice bearing breast cancer xenografts with MCF-7 cells (ip, 150 mg/kg/day, 16 days), can hinders Estrogen Receptor 1 transcription by targeting the ROS-FOXM1 axis and indirectly curtails the Wnt/β-catenin signaling pathway, thus stalling breast cancer cell proliferation ( Xu et al, 2022 ). Research by Qi et al (2016) highlighted that extracts derived from Auriculariaauricula (L.cxHook.…”