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

• Published in: Biomedicine & pharmacotherapy 2023-09, Vol.165, p.115221-115221, Article 115221
• Main Authors: Vachiraarunwong, Arpamas, Tuntiwechapikul, Wirote, Wongnoppavich, Ariyaphong, Meepowpan, Puttinan, Wongpoomchai, Rawiwan
• Format: Article
• Language: English
• Subjects: 4'-dihydroxy-6'-methoxy-3'; 5'-dimethylchalcone; Anticarcinogenicity; Cancer chemoprevention; Cleistocalyx nervosum var. paniala
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115221

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). 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. 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. 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. [Display omitted] •DMC isolated from C. nervosum seeds present chemopreventive activity in the early stages of colorectal carcinogenesis.•Colonic preneoplastic lesions were decreased by induction of drug metabolizing enzyme and reduction of cell proliferation.•DMC obtained from C. nervosum seeds could be a promising anticarcinogen.