Metallothionein Family Proteins as Regulators of Zinc Ions Synergistically Enhance the Anticancer Effect of Cannabidiol in Human Colorectal Cancer Cells

被引：5

作者：

Kwon, In-Seo ^{[1
]}

Hwang, Yu-Na ^{[1
]}

Park, Ju-Hee ^{[1
]}

Na, Han-Heom ^{[1
,2
]}

Kwon, Tae-Hyung ^{[3
]}

Park, Jin-Sung ^{[4
]}

Kim, Keun-Cheol ^{[1
,2
]}

机构：

[1] Kangwon Natl Univ, Coll Nat Sci, Dept Biol Sci, Chunchon 24341, Kangwon, South Korea

[2] Kangwon Ctr Syst Imaging, Chunchon 24341, Kangwon, South Korea

[3] Chuncheon Bioind Fdn, Chunchon 24232, Kangwon, South Korea

[4] Korean Pharmacopuncture Inst, Seoul 07525, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 23期

基金：

新加坡国家研究基金会;

关键词：

cannabidiol; colorectal cancers; cell death; metallothionein; zinc ion; APOPTOSIS; CANNABINOIDS; HOMEOSTASIS; EXPRESSION;

D O I：

10.3390/ijms242316621

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cannabidiol (CBD) is a chemical obtained from Cannabis sativa; it has therapeutic effects on anxiety and cognition and anti-inflammatory properties. Although pharmacological applications of CBD in many types of tumors have recently been reported, the mechanism of action of CBD is not yet fully understood. In this study, we perform an mRNA-seq analysis to identify the target genes of CBD after determining the cytotoxic concentrations of CBD using an MTT assay. CBD treatment regulated the expression of genes related to DNA repair and cell division, with metallothionein (MT) family genes being identified as having highly increased expression levels induced by CBD. It was also found that the expression levels of MT family genes were decreased in colorectal cancer tissues compared to those in normal tissues, indicating that the downregulation of MT family genes might be highly associated with colorectal tumor progression. A qPCR experiment revealed that the expression levels of MT family genes were increased by CBD. Moreover, MT family genes were regulated by CBD or crude extract but not by other cannabinoids, suggesting that the expression of MT family genes was specifically induced by CBD. A synergistic effect between CBD and MT gene transfection or zinc ion treatment was found. In conclusion, MT family genes as novel target genes could synergistically increase the anticancer activity of CBD by regulating the zinc ions in human colorectal cancer cells.

引用

页数：16

共 66 条

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