来自五桠果变种 nervosum 种子的 2,4'-二羟基-6'-甲氧基-3',5'-二甲氧基查尔酮可减轻二乙基亚硝胺和 1,2-二甲基肼诱导的结直肠肿瘤发生的早期阶段。

2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone from Cleistocalyx nervosum var. paniala seeds attenuated the early stage of diethylnitrosamine and 1,2-dimethylhydrazine-induced colorectal carcinogenesis.

机构信息

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.

出版信息

Biomed Pharmacother. 2023 Sep;165:115221. doi: 10.1016/j.biopha.2023.115221. Epub 2023 Jul 28.

DOI:10.1016/j.biopha.2023.115221

PMID:37517291

Abstract

BACKGROUND

Dichloromethane extract of Cleistocalyx nervosum var. paniala seeds exhibited an anticarcinogenicity against chemically-induced the early stages of carcinogenesis in rats. This study aimed to identify anticarcinogenic compounds from C. nervosum seed extract (CSE).

METHODS

Salmonella mutation assay was performed to determine mutagenicity and antimutagenicity of partially purified and purified compounds of CSE. The anticarcinogenic enzyme-inducing activity was measured in Hepa1c1c7. Moreover, the anticancer potency was examined on various human cancer cell lines. The anticarcinogenicity of DMC was investigated using dual-organ carcinogenicity model. The number of preneoplastic lesions was evaluated in the liver and colon. The inhibitory mechanisms of DMC on liver- and colorectal carcinogenesis were investigated.

RESULTS

Six partially purified fractions (MK1 - MK6) and purified compounds, including 2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) and hariganetin, were obtained from CSE. Among these fractions, MK4 and DMC presented the greatest antimutagenicity against indirect mutagens in bacterial model. Moreover, MK5 possessed an effective anticarcinogenic enzyme inducer in Hepa1c1c7. The MK4, DMC and CSE showed greater anticancer activity on all cell lines and exhibited the most effective toxicity on colon cancer cells. Furthermore, DMC inhibited the formation of colonic preneoplastic lesions in carcinogens-treated rats. It reduced PCNA-positive cells and frequency of BCAC in rat colon. DMC also enhanced the detoxifying enzyme, GST, in rat livers.

CONCLUSIONS

DMC obtained from CSE may be a promising cancer chemopreventive compound of colorectal cancer process in rats. It could increase detoxifying enzymes and suppress the cell proliferation process resulting in prevention of post-initiation stage of colorectal carcinogenesis.

摘要

背景

五桠果 var. paniala 种子的二氯甲烷提取物对化学诱导的大鼠致癌作用的早期阶段表现出抗癌作用。本研究旨在从五桠果种子提取物 (CSE) 中鉴定出抗癌化合物。

方法

采用沙门氏菌致突变试验测定 CSE 部分纯化和纯化化合物的致突变性和抗突变性。在 Hepa1c1c7 中测定抗癌酶诱导活性。此外，还在各种人癌细胞系上检查了抗癌能力。采用双器官致癌模型研究 DMC 的抗癌作用。在肝脏和结肠中评估了前肿瘤病变的数量。研究了 DMC 对肝和结直肠癌发生的抑制机制。

结果

从 CSE 中获得了六个部分纯化的馏分 (MK1-MK6) 和纯化的化合物，包括 2,4'-二羟基-6'-甲氧基-3',5'-二甲基查尔酮 (DMC) 和哈里根汀。在这些馏分中，MK4 和 DMC 在细菌模型中对间接诱变剂表现出最大的抗突变性。此外，MK5 在 Hepa1c1c7 中具有有效的抗癌酶诱导剂。MK4、DMC 和 CSE 对所有细胞系均表现出更强的抗癌活性，并对结肠癌细胞表现出最强的毒性。此外，DMC 抑制了致癌物处理大鼠结肠前肿瘤病变的形成。它减少了 PCNA 阳性细胞和大鼠结肠中 BCAC 的频率。DMC 还增强了大鼠肝脏中的解毒酶 GST。