PMID- 31412862 OWN - NLM STAT- MEDLINE DCOM- 20191216 LR - 20201019 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 19 IP - 1 DP - 2019 Aug 14 TI - Berberine inhibits NLRP3 Inflammasome pathway in human triple-negative breast cancer MDA-MB-231 cell. PG - 216 LID - 10.1186/s12906-019-2615-4 [doi] LID - 216 AB - BACKGROUND: 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. METHODS: 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). RESULTS: 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-1alpha (IL-1alpha), Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). 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-1beta proteins and NLRP3, Caspase-1 and ASC mRNAs in the NLRP3 inflammasome cascade. CONCLUSIONS: 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. FAU - Yao, Mingjiang AU - Yao M AD - Xiyuan Hospital of China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, No.1 Xiyuan Caochang, Haidian District, Beijing, 100091, China. AD - Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, China. FAU - Fan, Xiaodi AU - Fan X AD - Xiyuan Hospital of China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, No.1 Xiyuan Caochang, Haidian District, Beijing, 100091, China. AD - Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, China. FAU - Yuan, Bo AU - Yuan B AD - Laboratory of Pharmacology, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan. FAU - Takagi, Norio AU - Takagi N AD - Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. FAU - Liu, Sai AU - Liu S AD - Xiyuan Hospital of China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, No.1 Xiyuan Caochang, Haidian District, Beijing, 100091, China. AD - Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, China. FAU - Han, Xiao AU - Han X AD - Xiyuan Hospital of China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, No.1 Xiyuan Caochang, Haidian District, Beijing, 100091, China. AD - Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, China. FAU - Ren, Junguo AU - Ren J AD - Xiyuan Hospital of China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, No.1 Xiyuan Caochang, Haidian District, Beijing, 100091, China. AD - Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, China. FAU - Liu, Jianxun AU - Liu J AD - Xiyuan Hospital of China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, No.1 Xiyuan Caochang, Haidian District, Beijing, 100091, China. liujx0324@sina.com. AD - Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, China. liujx0324@sina.com. LA - eng GR - 81403141/Young Scientists Fund/ GR - 81873040/Major Research Plan/ PT - Journal Article DEP - 20190814 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Drugs, Chinese Herbal) RN - 0 (IL18 protein, human) RN - 0 (IL1B protein, human) RN - 0 (Inflammasomes) RN - 0 (Interleukin-18) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0I8Y3P32UF (Berberine) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Apoptosis/drug effects MH - Berberine/*pharmacology MH - Caspase 1/genetics/immunology MH - Drugs, Chinese Herbal/*pharmacology MH - Female MH - Humans MH - Inflammasomes/*drug effects/genetics/immunology MH - Interleukin-18/genetics/immunology MH - Interleukin-1beta/genetics/immunology MH - Interleukin-6/genetics/immunology MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*immunology MH - Triple Negative Breast Neoplasms/drug therapy/genetics/*immunology/physiopathology MH - Tumor Necrosis Factor-alpha/genetics/immunology PMC - PMC6694465 OTO - NOTNLM OT - Anti-inflammation OT - Berberine OT - NLRP3 inflammasome OT - Triple-negative breast cancer COIS- The authors declare that they have no competing interests. EDAT- 2019/08/16 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/08/14 CRDT- 2019/08/16 06:00 PHST- 2019/05/04 00:00 [received] PHST- 2019/07/23 00:00 [accepted] PHST- 2019/08/16 06:00 [entrez] PHST- 2019/08/16 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/08/14 00:00 [pmc-release] AID - 10.1186/s12906-019-2615-4 [pii] AID - 2615 [pii] AID - 10.1186/s12906-019-2615-4 [doi] PST - epublish SO - BMC Complement Altern Med. 2019 Aug 14;19(1):216. doi: 10.1186/s12906-019-2615-4.