Dihydroptychantol A, a macrocyclic bisbibenzyl derivative, induces autophagy and following apoptosis associated with p53 pathway in human osteosarcoma U2OS cells

被引:38
|
作者
Li, Xia [1 ,2 ]
Wu, William K. K. [3 ,4 ]
Sun, Bin [1 ]
Cui, Min [2 ]
Liu, Shanshan [2 ]
Gao, Jian [1 ]
Lou, Hongxiang [1 ]
机构
[1] Shandong Univ, Sch Pharmaceut Sci, Jinan 250012, Peoples R China
[2] Shandong Univ, Sch Ocean, Weihai 264209, Peoples R China
[3] Chinese Univ Hong Kong, Inst Digest Dis, LKS Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China
[4] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
Dihydroptychantol A; U2OS cells; p53; Autophagy; Apoptosis; MULTIDRUG-RESISTANCE; K562/A02; CELLS; CANCER-CELLS; PLAGIOCHIN-E; DEATH; ANTIFUNGAL; BIS(BIBENZYL)S; CYTOTOXICITY; MITOCHONDRIA; INHIBITION;
D O I
10.1016/j.taap.2010.12.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Dihydroptychantol A (DHA), a novel macrocyclic bisbibenzyl compound extracted from liverwort Asterella angusta, has antifungal and multi-drug resistance reversal properties. Here, the chemically synthesized DHA was employed to test its anti-cancer activities in human osteosarcoma U2OS cells. Our results demonstrated that DHA induced autophagy followed by apoptotic cell death accompanied with G(2)/M-phase cell cycle arrest in U2OS cells. DHA-induced autophagy was morphologically characterized by the formation of double membrane-bound autophagic vacuoles recognizable at the ultrastructural level. DHA also increased the levels of LC3-II, a marker of autophagy. Surprisingly, DHA-mediated apoptotic cell death was potentiated by the autophagy inhibitor 3-methyladenine, suggesting that autophagy may play a protective role that impedes the eventual cell death. Furthermore, p53 was shown to be involved in DHA-meditated autophagy and apoptosis. In this connection, DHA increased nuclear expression of p53, induced p53 phosphorylation, and upregulated p53 target gene p21(Waf1/Cip1). In contrast, cytoplasmic p53 was reduced by DHA, which contributed to the stimulation of autophagy. In relation to the cell cycle. DHA decreased the expression of cyclin B-1, a cyclin required for progression through the G(2)/M phase. Taken together, DHA induces G(2)/M-phase cell cycle arrest and apoptosis in U2OS cells. DHA-induced apoptosis was preceded by the induction of protective autophagy. DHA-mediated autophagy and apoptosis are associated with the cytoplasmic and nuclear functions of p53. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:146 / 154
页数:9
相关论文
共 50 条
  • [31] KAEMPFEROL INDUCES APOPTOSIS VIA MITOCHONDRIAL- AND CASPASE-DEPENDENT CASPASE SIGNALING PATHWAYS IN HUMAN OSTEOSARCOMA U2OS CELLS
    Huang, Wen-Wen
    Lin, Men-Wei
    Lin, Kuei-Li
    Ho, Wai-Jane
    Lin, Chin-Fen
    Li, Kun-Hong
    Yang, Jai-sing
    Chung, Jing-Gung
    ANTICANCER RESEARCH, 2008, 28 (5C) : 3322 - 3323
  • [32] A Novel Indolizine Derivative Induces Apoptosis Through the Mitochondria p53 Pathway in HepG2 Cells
    Liu, Yushuang
    Shao, Enxian
    Zhang, Zhiyang
    Yang, Daji
    Li, Guanting
    Cao, Hua
    Huang, Hongliang
    FRONTIERS IN PHARMACOLOGY, 2019, 10
  • [33] Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma cells via mitochondrial dysfunction
    Di, Weihua
    Khan, Muhammad
    Gao, Yong
    Cui, Jing
    Wang, Deqiang
    Qu, Mingfen
    Feng, Liangtao
    Maryam, Amara
    Gao, Hongwen
    MOLECULAR MEDICINE REPORTS, 2017, 15 (01) : 277 - 284
  • [34] A polysaccharide from Enterobacter cloacae induces apoptosis of human osteosarcoma cells through the activation of p53 and mitochondrial intrinsic pathway
    Chen, Haicong
    Wang, Chaojun
    Wang, Xin
    Guo, Zhen
    Xu, Zhujin
    Zhao, Yi
    Cai, Jiashang
    Liu, Jun
    INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2019, 122 : 58 - 63
  • [35] ONX-0914 Induces Apoptosis and Autophagy with p53 Regulation in Human Glioblastoma Cells
    Chang, Hsin-Han
    Lin, Yi-Hsuan
    Chen, Tzu-Min
    Tsai, Yu-Ling
    Lai, Chien-Rui
    Tsai, Wen-Chiuan
    Cheng, Yu-Chen
    Chen, Ying
    CANCERS, 2022, 14 (22)
  • [36] Neratinib derivative 7A induces apoptosis in colon cancer cells via the p53 pathway
    Liu, Zhi-Yu
    Liu, Ruo-Tong
    Cheng, Wen-Hao
    Zhang, Bo-Yu
    Zhang, Xing-Yu
    Zhou, Ying
    Ye, Xiao-Qing
    Zhou, Chun-Yun
    Wang, Xiu-Jun
    Sun, Qian
    Ji, Jing
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2025, 117
  • [37] Inorganic phosphate inhibits growth of human osteosarcoma U2OS cells via adenylate cyclase/cAMP pathway
    Naviglio, Silvio
    Spina, Annamaria
    Chiosi, Emilio
    Fusco, Anna
    Illiano, Fausto
    Pagano, Mario
    Romano, Maria
    Senatore, Giovanna
    Sorrentino, Annunziata
    Sorvillo, Luca
    Illiano, Gennaro
    JOURNAL OF CELLULAR BIOCHEMISTRY, 2006, 98 (06) : 1584 - 1596
  • [38] Apoptosis induced by adenovirus-mediated p14ARF expression in U2OS osteosarcoma cells is associated with increased Fas expression
    Kim, M
    Sgagias, M
    Deng, XY
    Jung, YJ
    Rikiyama, T
    Lee, K
    Ouellette, M
    Cowan, K
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 320 (01) : 138 - 144
  • [39] MicroRNA-190b inhibits tumor cell proliferation and induces apoptosis by regulating Bcl-2 in U2OS osteosarcoma cells
    Kang, Mingyang
    Xia, Peng
    Hou, Tingting
    Qi, Zhiping
    Liao, Shaojun
    Yang, Xiaoyu
    PHARMAZIE, 2017, 72 (05): : 279 - 282
  • [40] Bufalin induces apoptosis in the U-2OS human osteosarcoma cell line via triggering the mitochondrial pathway
    Chen, Ya
    Li, Meng
    Li, Zhongji
    Gao, Peng
    Zhou, Xiao
    Zhang, Jianxin
    MOLECULAR MEDICINE REPORTS, 2016, 13 (01) : 817 - 822