Active Ingredients from Euodia ruticarpa Steam Distilled Essential Oil Inhibit PC-3 Prostate Cancer Cell Growth via Direct Action and Indirect Immune Cells Conditioned Media In Vitro.

Tzu-He Yeh,Jin-Yuarn Lin

doi:10.3390/cimb43020071

Tzu-He Yeh, Jin-Yuarn Lin

Open Access

https://doi.org/10.3390/cimb43020071

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Abstract

Active constituents isolated from Euodia ruticarpa (ER) steam distilled essential oil (SDEO) against PC-3 prostate cancer cell growth remain unclear. To clarify the puzzle, ER SDEO was extracted and further resolved into six isolated fractions ERF1–F6 with Sephadex LH-20 gel filtration chromatography to analyze their biological activities. Active ingredients in the isolated fractions were analyzed with GC-MS. Potential isolated fractions were selected to treat PC-3 cells with direct action and indirect treatment by mouse splenocyte- (SCM) and macrophage-conditioned media (MCM). The relationship between PC-3 cell viabilities and corresponding total polyphenols, flavonoid contents as well as Th1/Th2 cytokine profiles in SCM was analyzed using the Pearson product–moment correlation coefficient (r). As a result, ERF1–F3 was abundant in total polyphenols and flavonoids contents with diverse active ingredients. Treatments with ERF1–F3 at appropriate concentrations more or less inhibit PC-3 cell growth in a direct action manner. Only SCM, respectively, cultured with ER SDEO and ERF1–F3 markedly enhanced the effects to inhibit PC-3 cell growth, suggesting that secretions by splenocytes might involve anti-PC-3 effects. There are significantly negative correlations between PC-3 cell viabilities and IL-2, IL-10 as well as IL-10/IL-2 ratios in the corresponding SCM. Total polyphenol and flavonoid contents in the media cultured with ER SDEO isolated fractions positively correlated with IL-10 (Th2) and IL-10/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, indicating that polyphenol and flavonoid components in ER SDEO isolated fractions promote Th2-polarized and anti-inflammatory characteristics. These new findings concluded that the inhibitory effects against PC-3 prostate cancer cell growth are attributed to active anti-inflammatory ingredients in ER SDEO and its active ERF1–F3 fractions through direct action and indirect treatment by modulating splenocytes’ cytokine secretion profiles.

Highlights

Prostate cancer is a heterogeneous malignant tumor that occurs in elderly men, mostly resulting from age, diet, hormones and genetics [1]
The results showed that all of isolated fractions are rich in polyphenols and flavonoids (Table 1), identical to our assumption based on Euodia ruticarpa (ER) steam distilled essential oil (SDEO) absorption spectra (Figure S1)
IL-1β, TNF-α, IL-6 and IL-10 secreted by macrophages were markedly increased by Euodia ruticarpa steam distilled essential oil (ER SDEO) and ERF1–F3

Summary

Introduction

Prostate cancer is a heterogeneous malignant tumor that occurs in elderly men, mostly resulting from age, diet, hormones and genetics [1]. Treatments for prostate cancers include castration therapy, radiation therapy, androgen deprivation therapy (ADT), chemotherapy and possible immunotherapy [2]. Testosterone, a hormone produced in the testicles, may further stimulate prostate hyperplasia in some patients [3]. Most advanced prostate cancer patients evolve an uncontrollable castration-resistant prostate cancer (CRPC), resulting in scantiness of hormones in the body and increasing the difficulty for prostate cancer treatments [4]. Cancer immunotherapy has been a promising method and shines a light on prostate cancer

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