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Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation involving the gut system, and disequilibrium of T helper (Th) cell paradigm has been recognized as critical pathogenesis. Pycnoporus sanguineus (L.) Murrill is a species of the white-rot basidiomycetes listed as food- and cosmetic-grade microorganisms. In this study, anti-inflammatory activity of the ethanol extract from P. sanguineus (PSE) was investigated in dextran sulfate sodium (DSS)-induced experimental colitis model. PSE recovered the DSS-caused weight loss, reversed the colon shortening, and ameliorated the histopathological lesion in colon, resulting in lower disease activity index (DAI). Levels of serumal lipopolysaccharide (LPS), colonic myeloperoxidase (MPO) in the colitis-suffering mice were declined by PSE treatment. PSE also improved the mucosal integrity by enhancing the expression of tight junction and adherens junction proteins in the colon, including ZO-1, occludin, claudin-1, and E-cadherin. Besides, PSE reduced helper T cells (Th) in the colon, together with an evident decrease of several Th cell-related cytokines. Moreover, it was found that in vitro, PSE suppressed T cells and the Th subset upon Concanavalin A (ConA)-stimulation by inducing apoptosis. In summary, PSE displayed a remission on the colitis-related inflammation, which would possibly rely on the epithelial barrier restoration by suppressing Th cells via apoptosis induction, highlighting a promising potential in the treatment for IBD.

Inflammatory bowel disease (IBD) is a chronic autoimmune disease associated with various risk factors. Pycnoporus sanguineus (L.) Murrill is a saprotrophic fungus used worldwide for its industrial and medical purposes. Here, polysaccharide from P. sanguineus (PPS) was explored for its antiinflammatory potential in a murine colitis model of IBD induced by dextran sulfate sodium (DSS). PPS ameliorated the colitis as manifested by the lowered disease activity index (DAI), prolonged colon, and reduced serum lipopolysaccharide (LPS). PPS recovered the histological lesion by upregulating the expressions of Zonula occludens-1 (ZO-1), E-cadherin, and proliferating cell nuclear antigen (PCNA). PPS inhibited the helper T cells (Th)-mediated immune response by decreasing the proportions of Th cells (including Th2 cells, Th17 cells, and regulatory T cells), which was accompanied with reductions on myeloperoxidase (MPO) activity and releases of several interleukins and chemokines within the colon. Moreover, PPS exhibited an evident inhibition on autophagy, in which the ratio of light chain 3 (LC3) II/I was declined, while the expression of p62 and Beclin-1 was increased. The present study highlighted important clinical implications for the treatment application of PPS against IBD, which relies on the regulation of Th cells repertoire and autophagy suppression to restore epithelium barrier.