Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
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DOI：
10.1371/journal.pone.0056020
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sultana S
中科院分区：
文献类型：
--
作者：
Khan R;Khan AQ;Lateef A;Rehman MU;Tahir M;Ali F;Hamiza OO;Sultana S
结肠癌的发生是一个多步骤的过程，它源于一系列的分子和组织病理学改变。甘草酸（GA）是甘草提取物中的一种主要的天然五环三萜苷。它具有多种药理学和生物学特性，如抗炎，抗病毒和抗癌。在本研究中，我们研究了GA对1，2-二甲基肼（DMH）诱导的癌前病变的化学预防潜力，即，异常隐窝灶（ACF）和粘蛋白缺失灶（MUC-DELESIVE FOCUS）的表达，探讨其在调节Wistar大鼠结肠过度增殖、炎症、血管生成和凋亡中的作用。动物分为5组。在III、IV和V组中，以15 mg/kg B的剂量给予GA。重量口服，而在组II、III和IV中，DMH以20 mg/kg B.wt的剂量在腹股沟皮下给药，每周一次，持续前5周，9周后对动物实施安乐死。GA可抑制癌前病变的发展，减少肥大细胞的浸润，抑制Ki-67、NF-κ B-p65、考克斯-2、iNOS和VEGF的表达，增强p53、connexin-43、caspase-9和cleaved caspase-3的表达。GA处理显著降低了TNF-α的水平，也减少了粘膜层的消耗，并减弱了唾液粘蛋白向硫粘蛋白的转移。我们的研究结果表明GA对DMH诱导的结肠癌发生具有很强的化学预防潜力，但需要进一步研究来阐明GA的确切作用机制。
Colon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA) is a natural and major pentacyclic triterpenoid glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions i.e., aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats. Animals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks. GA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin. Our findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
3.3
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Femia, Angelo Pietro;Giannini, Augusto;Caderni, Giovanna
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Caderni, Giovanna
影响因子：
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作者：
BIRD, RP
通讯作者：
BIRD, RP
影响因子：
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作者：
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通讯作者：
FILIPE, MI
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作者：
Curreli, F;Friedman-Kien, AE;Flore, O
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Flore, O