Botanical preparation HX109 inhibits macrophage-mediated activation of prostate epithelial cells through the CCL4-STAT3 pathway: implication for the mechanism underlying HX109 suppression of prostate hyperplasia

Seonung Lim; Hyun-Keun Kim; Wonwoo Lee; Sunyoung Kim

doi:10.1016/j.heliyon.2020.e04267

Botanical preparation HX109 inhibits macrophage-mediated activation of prostate epithelial cells through the CCL4-STAT3 pathway: implication for the mechanism underlying HX109 suppression of prostate hyperplasia

Heliyon. 2020 Jun 23;6(6):e04267. doi: 10.1016/j.heliyon.2020.e04267. eCollection 2020 Jun.

Authors

Seonung Lim¹, Hyun-Keun Kim¹, Wonwoo Lee², Sunyoung Kim²

Affiliations

¹ School of Biological Sciences, Seoul National University, Seoul, 151-742, Republic of Korea.
² Helixmith Co. Ltd., 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.

Abstract

Benign prostatic hyperplasia (BPH) is one of the most frequently observed diseases in the elderly male population worldwide. A variety of factors such as aging, hormonal imbalance, chronic inflammation, and oxidative stress play an important role in its pathogenesis. We have previously shown that HX109, an ethanol extract prepared from 3 plants (Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera), alleviates prostate hyperplasia in the BPH rat model and suppresses AR signaling by upregulating Ca²⁺/CAMKKβ and ATF3. In this study, we used macrophage cell lines to examine the effects of HX109 on inflammation, which is considered an important causative factor in BPH pathogenesis. In the co-culture system involving macrophage-prostate epithelial cells, HX109 inhibited macrophage-induced cell proliferation, migration and epithelial-mesenchymal transition (EMT) by inhibiting the expression of CCL4 and the phosphorylation of STAT3. Furthermore, HX109 inhibited the expression of inflammatory cytokines and the phosphorylation of p65 NF-κB in a concentration dependent manner. Taken together, our results suggested that HX109 could regulate macrophage activation and its crosstalk with prostate cells, thereby inhibiting BPH.

Keywords: Bioactive plant product; Biomolecules; Botany; CCL4; Cell biology; Cell culture; HX109; Inflammation; Macrophage; NF-κB; Natural product; Prostate epithelial cell; STAT3.