呫吨酮并吡啶衍生物XP-16对人鼻咽癌CNE细胞的体外抑制作用

广西师范大学学报（自然科学版） ›› 2014, Vol. 32 ›› Issue (2): 95-100.

呫吨酮并吡啶衍生物XP-16对人鼻咽癌CNE细胞的体外抑制作用

韩留玉^1,2, 戴支凯³, 杨政敏^1,2, 黄俊^1,2, 覃江克^1,2, 苏桂发^1,2

1. 广西师范大学化学与药学学院,广西桂林541004;
2. 广西师范大学药用资源化学与药物分子工程教育部重点实验室,广西桂林541004;
3. 桂林医学院药学院,广西桂林541004

收稿日期:2013-11-15 出版日期:2014-06-25 发布日期:2018-09-25
通讯作者: 覃江克(1977—),男,广西大化人,广西师范大学教授,博士。E-mail: jiangkeq@sina.com
基金资助:
国家自然科学基金资助项目(21002015);广西自然科学基金资助项目(2010GXNSFB013013, 0639030)

Inhibitory Action of a Xanthono-pyridine Derivative XP-16 on Human Nasopharyngeal Carcinoma CNE Cells in vitro

HAN Liu-yu^1,2, DAI Zhi-kai³, YANG Zheng-min^1,2, HUANG Jun^1,2, QIN Jiang-ke^1,2, SU Gui-fa^1,2

1. College of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin Guangxi 541004, China;
2. Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of State Education Ministry, Guangxi Normal University, Guilin Guangxi 541004, China;
3. College of Pharmaceutical Science, Guilin Medical University, Guilin Guangxi 541004, China

Received:2013-11-15 Online:2014-06-25 Published:2018-09-25

摘要/Abstract

摘要： 运用MTT法、细胞形态学观察和细胞克隆实验观察一个新型的呫吨酮并吡啶衍生物(XP-16)对人鼻咽癌CNE细胞的体外抗肿瘤效应;运用Hoechest33258和PI双染、流式细胞仪检测、荧光光度法、RT-PCR等手段研究其可能的作用机制。结果表明,该化合物能剂量和时间依赖性地抑制CNE细胞增殖;XP-16作用于CNE细胞24 h后,CNE细胞出现染色质聚集、核碎裂等典型的凋亡形态学改变,且随化合物剂量的增加,CNE细胞凋亡百分率逐渐增大;CNE细胞阻滞于G2-M和S期;并且引起CNE细胞线粒体膜电位降低、Bad和MT-1A的mRNA表达增加。XP-16具有诱导CNE细胞凋亡作用,其作用机制可能与其降低线粒体膜电位、上调MT-1A表达有关。

关键词: 呫吨酮, 抗肿瘤, 人鼻咽癌CNE细胞, 凋亡

Abstract: MTT assay, morphological examination and colonial assay were applied to evaluate the antiproliferative effect of a new xanthono-pyridine derivative (XP-16) on human nasopharyngeal carcinoma CNE cells; Hoechest 33258/PI double staining, flow cytometry, spectrofluorimetry and RT-PCR were also employed to investigate its possible action mechanism. The experiment results showed that XP-16 could inhibit the proliferation of CNE cells in dose- and time-dependent manner. Typical apoptotic morphology such as chromatin aggregation and nuclear fragmentation was observed in XP-16 treated CNE cells for 24 h in a dose-dependent manner. After treated with XP-16, CNE cells were blocked in G2-M and S phases, mitochondria membrane potential of the cells was decreased, relative Bad and MT-1A mRNA level was up-regulated. The apoptosis of CNE cells inducing by XP-16 might be associated with decreasing mitochondria membrane potential and up-regulating MT-1A.

Key words: xanthone, antitumor, human nasopharyngeal carcinoma cell line CNE, apoptosis

中图分类号:

R962

韩留玉, 戴支凯, 杨政敏, 黄俊, 覃江克, 苏桂发. 呫吨酮并吡啶衍生物XP-16对人鼻咽癌CNE细胞的体外抑制作用[J]. 广西师范大学学报（自然科学版）, 2014, 32(2): 95-100.

HAN Liu-yu, DAI Zhi-kai, YANG Zheng-min, HUANG Jun, QIN Jiang-ke, SU Gui-fa. Inhibitory Action of a Xanthono-pyridine Derivative XP-16 on Human Nasopharyngeal Carcinoma CNE Cells in vitro[J]. Journal of Guangxi Normal University(Natural Science Edition), 2014, 32(2): 95-100.

参考文献

[1] FOTIE J, BOHLE D S. Pharmacological and biological activities of xanthones[J]. Anti-infect Agents Med Chem, 2006, 5(1): 15-31.
[2] NA Y. Recent cancer drug development with xanthone structures[J]. J Pharm Pharmacol, 2009, 61(6): 707-712.
[3] AZEVEDO C M G, AFONSO C M M, SOARES J X, et al. Pyranoxanthones: Synthesis, growth inhibitory activity on human tumor cell lines and determination of their lipophilicity in two membrane models[J]. Eur J Med Chem, 2013, 69(11): 798-861.
[4] LAN Wen-li, WEI Jing-chen, QIN Jiang-ke, et al. Synthesis and biological evaluation of 1, 3-dihydroxyxanthone mannich base derivatives as potential antitumor agents[J]. Lett Drug Des Discov, 2013, 10(8): 689-698.
[5] LUO Lin, QIN Jiang-ke, DAI Zhi-kai, et al. Synthesis and biological evaluation of novel benzoxanthone derivatives as potential antitumor agents[J]. J Serb Chem Soc, 2013, 78(9): 1301-1308.
[6] 覃江克, 韩留玉, 杨政敏, 等. 胺基烷酰胺基呫吨酮并吡啶衍生物及其制备方法和应用:中国,200910114144.9[P]. 2011-04-27.
[7] LY J D, GRUBB D R, LAWEN A. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update[J]. Apoptosis, 2003, 8(2):115-128.
[8] WILLIS S N, CHEN Lin, DEWSON G, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins[J]. Genes Dev, 2005, 19(11): 1294-1305。
[9] WEI M C, ZONG Wei-xing, CHENG E H, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death[J]. Science, 2001, 292(5517): 727-730.
[10] CHATTOPADHYAY A, CHIANG Chi-wu, YANG E. BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest[J]. Oncogene, 2001, 20(33): 4507-4518.
[11] YAP X, TAN Hong-yong, HUANG Jing-xiang, et al. Over-expression of metallothionein predicts chemoresistance in breast cancer[J]. J Pathol, 2009, 217(4):563-570.
[12] KRIZKOVA S, MASARIK M, MAJZLIK P, et al. Serum metallothionein in newly diagnosed patients with childhood solid tumours[J]. Acta Biochim Pol, 2010, 57(4): 561-566.
[13] MAJUMDER S, ROY S, KAFFENBERGER T, et al. Loss of metallothionein predisposes mice to diethylnitrosamine-induced hepatocarcinogenesis by activating NF-kappaB target genes[J]. Cancer Res, 2010, 70(24): 10265-10276.
[14] KONDO Y, RUSNAK J M, HOYT D G, et al. Enhanced apoptosis in metallothionein-null cells[J]. Mol Pharmacol, 1997, 52(2): 195-201.
[15] CHERIAN M G, JAYASURYA A, BAY B H. Metallothioneins in human tumors and potential roles in carcinogenesis[J]. Mutat Res, 2003, 533(1/2): 201-209.
[16] SHIMODA R, ACHANZAR W E, QU Wei, et al. Metallothionein is a potential negative regulator of apoptosis[J]. Toxicol Sci, 2003, 73(2): 294-300.
[17] JIN Rong-xian, HUANG Jing-xiang, TAN P H, et al. Clinicopathological significance of metallothioneins in breast cancer[J]. Pathol Oncol Res, 2004, 10(2): 74-79.
[18] 戴支凯, 黄大林, 石京山, 等. 丹参酮ⅡA诱导人鼻咽癌CNE细胞凋亡[J]. 中国中药杂志, 2011, 36(15): 2129-2133.

相关文章 12

[1]	孙立, 初相伍, 刘春梅, 张琚政, 程克光. 熊果酸/甘草次酸-尿嘧啶核苷缀合物的合成与抗肿瘤活性评价[J]. 广西师范大学学报（自然科学版）, 2020, 38(1): 87-92.
[2]	孟春梅, 陆世银, 梁永红, 莫肖敏, 李卫东, 黄远洁, 成晓静, 苏志恒, 郑华. 岩黄连总碱诱导肝星状细胞凋亡和自噬的电镜实验研究[J]. 广西师范大学学报（自然科学版）, 2018, 36(3): 76-79.
[3]	刘茜. 南方红豆杉提取物的抗氧化、抗肿瘤活性研究[J]. 广西师范大学学报（自然科学版）, 2016, 34(4): 55-59.
[4]	吴亦明, 李亮萍, 曾淑兰, 李晓红, 周祖平, 彭艳. 1,8-萘二甲酰亚胺衍生物NA-17对肝癌细胞株HepG2的体外抗肿瘤作用研究[J]. 广西师范大学学报（自然科学版）, 2016, 34(3): 102-108.
[5]	黄婉云, 殷鹏龙, 李虹, 彭湘艳, 苏桂发. 喹诺酮-二茂铁杂合物的合成及生物活性研究[J]. 广西师范大学学报（自然科学版）, 2016, 34(2): 111-115.
[6]	梅寒冰, 王威, 姚雪, 程联彪, 黄瑾. Hsp90抑制剂木犀草苷对非小细胞肺癌的体外抑制活性及作用机理研究[J]. 广西师范大学学报（自然科学版）, 2015, 33(3): 91-97.
[7]	霍红月, 李仲庆, 覃其品, 刘延成, 陈振锋. 邻香草醛缩胡椒乙胺席夫碱锌(Ⅱ)配合物的研究[J]. 广西师范大学学报（自然科学版）, 2014, 32(3): 65-73.
[8]	陈思园, 杨扬, 彭艳, 刘延成. 一种新型希夫碱钯配合物的晶体结构及抗肿瘤活性研究[J]. 广西师范大学学报（自然科学版）, 2013, 31(2): 81-86.
[9]	刘观艳, 程克光, 邓胜平, 刘延成, 初相伍, 陈健辉, 马璐. 雌二醇酯类衍生物的合成与抗肿瘤活性研究[J]. 广西师范大学学报（自然科学版）, 2013, 31(1): 62-66.
[10]	唐煌, 王志宇, 钟书明, 覃江克. 6-取代1-氮杂苯并蒽酮衍生物的合成及抗肿瘤活性研究[J]. 广西师范大学学报（自然科学版）, 2012, 30(2): 78-82.
[11]	郭艳菊, 彭峰林. 黄酮对力竭运动大鼠心肌抗氧化与细胞凋亡的影响[J]. 广西师范大学学报（自然科学版）, 2012, 30(2): 143-148.
[12]	聂岳坤, 潘成学, 戴支凯, 苏桂发. 苯并菲啶类化合物的合成与生物活性研究[J]. 广西师范大学学报（自然科学版）, 2012, 30(1): 60-66.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed