Nat Commun:绿茶竟可增强p53的抗癌活性?

2021-02-12 MedSci原创 MedSci原创

人类与癌症的战斗由来以久,至今仍难以攻克,

人类与癌症的战斗由来以久,至今仍难以攻克,据世界卫生组织(WHO)数据显示,癌症发病率在逐年上升,全球每年新增癌症患者超过1400万,每年因癌症死亡的人数达880万。目前,癌症的常规治疗手段有限,包括外科手术、放射治疗以及化学药物等,其中药物的治疗可能还会导致严重副作用以及耐药,因此,寻找天然的副作用小的抗癌药物刻不容缓。

诸多研究证实,绿茶的多酚类物质具有抗癌的功效。儿茶素类是绿茶中主要的多酚类物质,具有多种生物活性,其中表没食子儿茶素没食子酸酯(epigallocatechin-3-gallateEGCG)约占绿茶儿茶素总量的80%,并且生物活性最高。近日,发表在Nature Communications杂志的一项研究显示,绿茶中的EGCG可能会增强p53的抗癌活性。p53是一种天然的抗癌基因,因其修复DNA损伤或破坏癌细胞的能力而被称为基因组守护者

研究人员发现,EGCG破坏了p53-MDM2的相互作用并抑制了由MDM2介导的p53的泛素化。通常情况下,p53在体内产生后,当N端域与MDM2的蛋白质相互作用时,会迅速被降解。这种有规律的生产和降解循环使p53的水平保持在一个较低的恒定值。然而,EGCGMDM2都在p53的同一个结合位点,即无序的N末端结构域(NTD),EGCGMDM2形成竞争。当EGCGp53结合时,蛋白质并没有通过MDM2被降解,所以与EGCG直接相互作用后,p53的水平会增加。

EGCG通过与p53的N末端结合来破坏p53-MDM2的相互作用

另外,EGCGp53–NTD之间的相互作用是高度动态的,涉及多个结合界面。众所周知,NTD是抗癌药物发现的靶点。一种MW值为458 Da的小分子EGCG可以有效地破坏p53MDM2之间的相互作用,并具有动态界面。以往旨在破坏p53-MDM2的药物发现主要集中在MDM2表面的NTD结合口袋。该数据表明,p53NTD也可能是小分子癌症药物发现的良好靶点。

总之, EGCG直接与肿瘤抑制因子p53结合,这为抗癌药物开发指明了一条新途径。

原始出处

Jing ZhaoAlan Blayney.et al.EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction.Nature Communications (2021). DOI: 10.1038/s41467-021-21258-5

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    2021-07-28 liuli5079
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    2021-08-11 JZ Yang

    绿茶

    0

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  4. [GetPortalCommentsPageByObjectIdResponse(id=2087911, encodeId=5e09208e911bd, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Wed Jul 28 14:54:11 CST 2021, time=2021-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1006896, encodeId=c3ff100689678, content=绿茶, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJibu7hwJqpmHiaJgLLmJmcwp0WDTxWI3vqPBO1Mloq21VBOPqziapyibYatvd2QWHWicolL1vbVZHgpRQ/132, createdBy=d16a2107341, createdName=JZ Yang, createdTime=Wed Aug 11 10:27:13 CST 2021, time=2021-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004024, encodeId=be8f10040244f, content=<a href='/topic/show?id=957ce9191f1' target=_blank style='color:#2F92EE;'>#绿茶#</a>能抗<a href='/topic/show?id=d8dbe130197' target=_blank style='color:#2F92EE;'>#癌症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79191, encryptionId=957ce9191f1, topicName=绿茶), TopicDto(id=71301, encryptionId=d8dbe130197, topicName=癌症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=小小医者, createdTime=Fri Jul 30 21:59:52 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884975, encodeId=81a418849e50d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Aug 17 08:54:11 CST 2021, time=2021-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372445, encodeId=b38c13e244518, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Sun Feb 14 14:54:11 CST 2021, time=2021-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1402410, encodeId=03a91402410be, content=<a href='/topic/show?id=862e8e196a1' target=_blank style='color:#2F92EE;'>#茶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87196, encryptionId=862e8e196a1, topicName=茶)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/eTyQ1TyLVfyaGrflWSd1Jw4u1F68ibicmN32DE38FjEW3zTIKeFeaMUAQsjyqaL4QZ3lRibFIzziacMz9niceznOTTw/132, createdBy=03082405249, createdName=hbwxf, createdTime=Sun Feb 14 14:54:11 CST 2021, time=2021-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=924360, encodeId=cd8d9243601b, content=这....拭目以待, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210127/50a003c4097845e182c08afd64d8a509/bd766dfebe9c40e0bca2dae964601bdc.jpg, createdBy=22de5454917, createdName=carrotlyl, createdTime=Sat Feb 13 06:52:03 CST 2021, time=2021-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=924353, encodeId=68d892435372, content=多喝茶有益健康, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b7a31928393, createdName=学医无涯, createdTime=Sat Feb 13 01:14:56 CST 2021, time=2021-02-13, status=1, ipAttribution=)]
    2021-08-17 liye789132251
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    2021-02-14 zhishijing
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    2021-02-14 hbwxf
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    2021-02-13 carrotlyl

    这....拭目以待

    0

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    2021-02-13 学医无涯

    多喝茶有益健康

    0

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