The inhibitory effects of compound Muniziqi granule against B16 cells and harmine induced autophagy and apoptosis by inhibiting Akt/mTOR pathway.
The inhibitory effects of compound Muniziqi granule against B16 cells and harmine induced autophagy and apoptosis by inhibiting Akt/mTOR pathway.
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DOI：
10.1186/s12906-017-2017-4
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发表时间：
2017-12-02
影响因子：
--
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Zou N;Wei Y;Li F;Yang Y;Cheng X;Wang C
复方木子气颗粒（MNZQ）是一种多成分草药制剂，是中国流行的维吾尔族传统药物，用于治疗内分泌失调引起的痤疮、黄褐斑、痛经、更年期综合征和黑色素瘤。MNZQ中存在的毒碱已被证实对B16细胞具有潜在的抗癌作用。本研究旨在探讨MNZQ对B16细胞的抑制作用，以及毒芹碱诱导B16细胞自噬和凋亡的机制。CCK8法计算细胞活力。用分光光度法测定体外酪氨酸酶活性。电镜和MDC染色证实了毒胺诱导的自噬。流式细胞术检测细胞死亡和细胞周期分布。western blot检测蛋白表达。与曲酸相比，MNZQ和部分草药提取物对B16细胞有抑制作用，但对蘑菇酪氨酸酶无抑制作用。毒鼠碱显著诱导B16细胞自噬体的形成，使LC3-II增加，p62退化，提示毒鼠碱是一种自噬诱导剂。细胞死亡和亚g2群体表明，害人碱可诱导细胞死亡。特别是，3-MA，一种自噬抑制剂，被发现可以防止harm诱导的细胞活力下降和细胞周期阻滞在G2期，这表明自噬对细胞死亡至关重要。此外，结果表明，毒芹碱可以抑制Akt和mTOR的磷酸化，这可能介导自噬。毒碱可通过抑制Akt/mTOR通路诱导B16细胞自噬和凋亡。毒碱可能是一种很有前途的治疗MNZQ黑色素瘤的药物。
Compound Muniziqi granule (MNZQ) is a multi-component herbal preparation and a popular traditional Uighur medicine used in China for treating endocrine disorder-induced acne, chloasma, dysmenorrhea, menopausal syndrome, and melanoma. Harmine presented in MNZQ has been confirmed potential anticancer effect on the B16 cells among others. The purpose of this study is to explore the inhibitory effects of MNZQ against B16 cells and mechanism of autophagy and apoptosis induced by harmine in B16 cells. The cell viability was calculated by CCK8 assay. The in vitro tyrosinase activity was determined by spectrophotometry. The harmine-induced autophagy was demonstrated by electron microscopy and MDC staining. Flow cytometry was used to measure cell death and cell cycle distribution. All proteins expression was assessed by western blot. MNZQ and some herb extracts contained in preparation displayed inhibitory effects on B16 cells but without inhibition on mushroom tyrosinase compared with kojic acid. The formation of autophagosome was markedly induced by harmine with the accretion of LC3-II and the degeneration of p62 in B16 cells, which indicated that harmine was an autophagy inducer. Cell death and sub-G2 population suggested that harmine could induce cell death. Particularly, 3-MA, an autophagy inhibitor, was discovered to prevent harmine-induced decrease of the cell viability and cell cycle arrest on G2 phase, indicating that autophagy was vital to the cell death. In addition, the results indicated that harmine could inhibit the phosphorylation of Akt and mTOR, which might mediate autophagy. Harmine could induce autophagy and apoptosis by inhibiting Akt/mTOR pathway in B16 cells. Harmine might be a promising therapeutic agent for treatment of melanoma in MNZQ.
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影响因子：
6.7
作者：
Fan, ChuanDong;Su, Hua;Miao, JunYing
通讯作者：
Miao, JunYing
影响因子：
--
作者：
Lippai M;Lőw P
通讯作者：
Lőw P
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1016/s1499-3872(11)60102-1
发表时间：
2011-12-01
影响因子：
3.3
作者：
Cao, Ming-Rong;Li, Qiang;Jiang, Jian-Wei
通讯作者：
Jiang, Jian-Wei
影响因子：
11.4
作者：
Eom, Hyun-Jeong;Choi, Jinhee
通讯作者：
Choi, Jinhee