Saikosaponin A Inhibits Breast Cancer by Regulating Th1/Th2 Balance

Abstract

Saikosaponin A (SSa) is isolated from the dried root of Radix Bupleuri , an herb widely used in traditional Chinese medicine, exerting antitumor activities. The T helper cell type 1(Th1)/Th2 balance is associated with antitumor immunity in breast cancer. The present study aimed to investigate the effects of SSa on Th1/Th2 balance in breast cancer and to explore the underlying mechanisms. Breast cancer in rats was induced by intragastrical administration of 7,12-dimethyl-benz[a] anthracene once (100 mg/kg). At d 91 , the rats suffering from tumors were randomly divided into three groups and treated with vehicle solution (control group), tamoxifen (TAM group), and SSa (SSa group) daily for 56 days, respectively. The tumor volume reduction ratio and tumor cell proliferation were detected to assess the antitumor effect of SSa. The positive staining numbers of CD8+ and CD4+ T cells infiltrated in breast tumors were measured by immunohistochemistry to evaluate the antitumor immunity of SSa. Cytokine levels in serum secreted by Th1 cells [interferon gamma (IFN-γ), interleukin (IL)-12] and Th2 cells (IL-4, IL-10) were detected to evaluate Th1/Th2 balance. The related molecules of IL-12/signal transducers and activators of transcription 4 (STAT4) pathway were detected by immunohistochemistry staining, RT-PCR, and Western blot to explore the mechanisms of SSa. The results showed that, compared with the control group, SSa significantly inhibited tumor growth and tumor cell proliferation. SSa enhanced antitumor immunity, which was demonstrated as increased CD8+ T cells and CD4+ T cells infiltrated in tumors. SSa shifted Th1/Th2 balance toward Th1, which was confirmed as increased serum IFN-γ and IL-12 levels, while decreased serum IL-4 and IL-10 levels. SSa increased IL-12, IL-12 receptor, and phosphorylated STAT4 expressions to promote Th1 differentiation. In conclusion, the present work suggested that SSa could inhibit breast cancer growth by shifting Th1/Th2 balance toward Th1. The underlying mechanism may involve activation of the IL-12/STAT4 pathway that induced Th1 differentiation.

Network Pharmacology and Molecular docking Analysis on Mechanisms and Molecular Targets of LongChaiJiangXue Formula for Treatment of Polycythemia Vera

“…It was found that kaempferol played an important role in anti-inflammation and anti-tumor aspects through JAK2 signaling and NF-κB signaling pathway [33]. Saikosaponin A was not only an anti-stress regulator [34] but also an anti-cancer agent [35]. Moreover, ursolic acid in GRR had a strong effect on inducing apoptosis through JAK2/STAT3 in colorectal cancer cells [36].…”

“…In this study, network pharmacology was applied to evaluate a TCM compound LCJX for the management of PV and seeking out its molecular targets, to provide a basis for further research on the mechanism. [19], atractylenolide III [20]in AMK, isoliquiritigenin [21], saikosaponin A [22]in RB, puerarin [23] in RB and GRR, ursolic acid [24] in GRR. have shown similar pharmalogical effects with the disease and were also selected.…”

Combination Vaccination With Tetanus Toxoid and Enhanced Tumor-Cell Based Vaccine Against Cervical Cancer in a Mouse Model

“…Th1 cell and Th2 cell immunity is critically important for the induction of anti-tumor cellular immunity (32,33). Th1 cells secrete cytokines such as IFN-γ, TNF-α/β, IL-2, and IL-10 (34).…”

The effect of dietary supplementation of Nigella sativa (black seeds) on cell mediated immunological function of male Wistar rats

“…6A242, Santa Cruz, CA, USA) at dilution rates 1:1000 and 1:200, respectively. The procedures were performed secondary polyvalent Biotinylated antibody according to the methodology of Zhao et al and Elgawish et al 60,61 , respectively. The percentages of the IHC-stained area (IHC area %) were acquired via ImageJ software as described by Elgawish and Abdelrazek 61 .…”