Breast cancer is still the most common malignant tumor that threatens the female’s life in the world, especially triple-negative breast cancer (TNBC), one of the most difficult subtypes. Lack of targeted therapies brings about urgent demand for novel treatments. In this study we aim to investigate the anti-tumor activity of Berberine (BBR), a Chinese plant-derived alkaloid, against the TNBC cell line MDA-MB-231 and elucidate its mechanism referring to anti-inflammation. Cell inhibition rate was measured by Cell Proliferation Assay, the cytotoxic effects was detected by Lactate dehydrogenase (LDH) leakage assay, the colony formation and migration potential were evaluated by colony formation assay and wound healing assay, the release of inflammatory cytokines was detected by EMD multifactor detection, and alterations of proteins and genes related to the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway were analyzed using western blotting and real-time Polymerase Chain Reaction (PCR). BBR reduce the viability of MDA-MB-231 cells and increased the release of LDH from the cells in a dose-dependent manner, with and inhibition of colony formation potential and migration of the cells. BBR also caused a marked reduction in the secretion of proinflammatory cytokines, Interleukin-1α (IL-1α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Besides, a down-regulated behavior was observed with the expression of P2X purinoceptor 7 (P2X7), NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1 p20, Interleukin-18 (IL-18), IL-1β proteins and NLRP3, Caspase-1 and ASC mRNAs in the NLRP3 inflammasome cascade. Our results confirmed that BBR can effectively affect both tumor outgrowth and spontaneous metastasis in TNBC, and that we identified a new mechanism associated with inhibition the NLRP3 inflammasome pathway, suggesting its potential therapeutic relevance in clinical use.

Betulinic acid (BA) is a natural product extracted from a broad range of medicinal and edible herbal plants. Previous studies showed that BA induces cell death in tumors derived from multiple tissues; however, the underlying mechanism remains obscure. The present study aimed to study the effects of BA on autophagy and apoptosis of hepatocellular carcinoma (HCC). Human HCC cell lines and orthotopic HCC implanted mice were employed to examine the BA‐induced tumor suppression; RT² long noncoding RNA (lncRNA) PCR array and database analysis were used to explore the possible mechanisms; validation of pathways was performed using siRNA and miRNA inhibitors. The results indicated that BA regulated autophagy and induced apoptosis in HCC. The degradation of inhibitor of apoptosis proteins (IAPs), the conversion of LC3‐I to LC3‐II, and p62 accumulation were enhanced by BA, thereby suggesting that the downregulation of IAPs and autophagic cell death are induced by BA. The addition of autophagy and lysosomal inhibitors indicated that BA induced autophagy‐independent apoptosis via degradation of IAPs. Moreover, RT² lncRNA PCR array and database analysis suggested that BA downregulated the levels of lncRNA MALAT1, which is considered to be an oncogene. Further investigations demonstrated that lncRNA MALAT1 functioned as a ceRNA (competing endogenous RNA) to contribute to BA‐mediated degradation of IAPs by sponging miR‐22‐3p. Therefore, BA could be developed as a potential anticancer agent for HCC.