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

Arpamas Vachiraarunwong; Wirote Tuntiwechapikul; Ariyaphong Wongnoppavich; Puttinan Meepowpan; Rawiwan Wongpoomchai

doi:10.1016/j.biopha.2023.115221

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

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

Authors

Arpamas Vachiraarunwong¹, Wirote Tuntiwechapikul², Ariyaphong Wongnoppavich³, Puttinan Meepowpan⁴, Rawiwan Wongpoomchai⁵

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: arpamas.c@gmail.com.
² Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: wirote.t@cmu.ac.th.
³ Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: ariyaphong.w@cmu.ac.th.
⁴ Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: pmeepowpan@gmail.com.
⁵ Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: rawiwan.wong@cmu.ac.th.

PMID: 37517291
DOI: 10.1016/j.biopha.2023.115221

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.

Keywords: 2'; 4'-dihydroxy-6'-methoxy-3'; 5'-dimethylchalcone; Anticarcinogenicity; Cancer chemoprevention; Cleistocalyx nervosum var. paniala.

MeSH terms

1,2-Dimethylhydrazine / toxicity
Animals
Carcinogenesis
Colorectal Neoplasms* / chemically induced
Colorectal Neoplasms* / prevention & control
Diethylnitrosamine
Humans
Rats
Seeds
Syzygium*

Substances

Diethylnitrosamine
1,2-Dimethylhydrazine