Abstract
Purpose: To investigate the involvement of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) in the pathogenesis of breast cancer in vivo as well as the activity of ten Chinese herbal compounds in human breast cancer (MCF-7) cell proliferation in vitro.Methods: In the in vivo study, the association of serum TNF-α and IL-10 with breast cancer cell invasiveness and prognosis was determined in female patients (n = 192) with breast cancer, while in the in vitro study, ten herbal Chinese compounds were screened for their effectiveness against MCF-7 cells. The levels of TNF-α, IL-10, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) were assayed using their respective enzyme-linked immunosorbent assay (ELISA) kits. Molecular docking was used to determine the lead compound(s) that can effectively inhibit TNF-α and IL-10.Results: Raised serum levels of TNF-α and IL-10 were significantly associated with breast cancer cell invasiveness and poor prognosis (p < 0.05). Moreover, there was a strong association between breast cancer prognosis and the expression levels of ER, PR and HER2/neu. Serum TNF-α and IL-10 levels were significantly elevated in stages II and III patients and in those with lymph node metastasis. Treatment of MCF-7 cells with the herbal compounds significantly reduced the synthesis and release of TNF-α and IL-10 (p < 0.05). The results of molecular docking showed that baicalein and oridonin significantly inhibited TNF- α and IL-10. The two herbal compounds had the highest docking scores for inhibition of cytokines, as well as favorable interaction energies.Conclusion: These results indicate that TNF-α and IL-10 are involved in the pathogenesis of breast cancer, and that baicalein and oridonin effectively inhibit the proliferation of the cells.
 Keywords: Baicalein, Breast cancer, Interleukin 10, Oridonin, Tumor necrosis factor alpha
Highlights
Breast cancer, the most frequently diagnosed life-threatening cancer in women, is the leading cause of cancer death among women [1]
The present study investigated the involvement of Tumor necrosis factor α (TNF-α) and Interleukin 10 (IL-10) in the pathogenesis of breast cancer in vivo, as well as the effectiveness of ten Chinese herbal compounds on MCF-7 cell proliferation in vitro
The results showed that elevated serum levels of TNF-α and IL-10 were significantly associated with breast cancer cell invasiveness and poor prognosis
Summary
The most frequently diagnosed life-threatening cancer in women, is the leading cause of cancer death among women [1]. Interleukin 10 (IL-10) is a cytokine with multiple, pleiotropic effects on immuno-regulation and inflammation. It downregulates the expression of T helper 1 (Th1) cytokines, major histocompatibility (MHC) class II antigens, and co-stimulatory molecules on macrophages. It enhances B cell survival, proliferation, and antibody production. It has been reported that upregulation of IL–10 expression reduces the chances of survival of breast cancer patients [15, 16]. The aim of this study was to investigate the involvement of TNF-α and IL-10 in the pathogenesis of breast cancer in vivo as well as the effectiveness of ten Chinese herbal compounds on MCF-7 cell proliferation in vitro
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