Anti-cancer activity of amorphous curcumin preparation in patient-derived colorectal cancer organoids

被引：41

作者：

Elbadawy, Mohamed ^{[1
,2
]}

Hayashi, Kimika ^{[1
]}

Ayame, Hiromi ^{[1
]}

Ishihara, Yusuke ^{[1
]}

Abugomaa, Amira ^{[1
,3
]}

Shibutani, Makoto ^{[4
]}

Hayashi, Shim-Mo ^{[4
]}

Hazama, Shoichi ^{[5
,6
]}

Takenouchi, Hiroko ^{[6
]}

Nakajima, Masao ^{[6
]}

Tsunedomi, Ryouichi ^{[6
]}

Suzuki, Nobuaki ^{[6
]}

Nagano, Hiroaki ^{[6
]}

Shinohara, Yuta ^{[1
,7
]}

Kaneda, Masahiro ^{[8
]}

Yamawaki, Hideyuki ^{[9
]}

Usui, Tatsuya ^{[1
]}

Sasaki, Kazuaki ^{[1
]}

机构：

[1] Tokyo Univ Agr & Technol, Fac Agr, Cooperat Dept Vet Med, Lab Vet Pharmacol, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan

[2] Benha Univ, Fac Vet Med, Dept Pharmacol, Toukh 13736, Elqaliobiya, Egypt

[3] Mansoura Univ, Fac Vet Med, Mansoura 35516, Dakahliya, Egypt

[4] Tokyo Univ Agr & Technol, Fac Agr, Cooperat Dept Vet Med, Lab Vet Pathol, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan

[5] Yamaguchi Univ, Sch Med, Dept Translat Res & Dev Therapeut Canc, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan

[6] Yamaguchi Univ, Grad Sch Med, Dept Gastroenterol Breast & Endocrine Surg, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan

[7] Iskara Ind CO LTD, Pet Hlth & Food Div, Chuo Ku, 1-14-2 Nihonbashi, Tokyo 1030027, Japan

[8] Tokyo Univ Agr & Technol, Fac Agr, Cooperat Dept Vet Med, Lab Vet Anat, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan

[9] Kitasato Univ, Sch Vet Med, Lab Vet Pharmacol, 35-1 Higashi 23 Ban Cho, Towada, Aomori 0348628, Japan

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2021年 / 142卷

基金：

日本学术振兴会;

关键词：

Colorectal cancer; Amorphous curcumin; Chemotherapy; Organoid; CSCs; Cell cycle; Apoptosis; C-MYC; ENHANCED BIOAVAILABILITY; CHEMOPREVENTIVE AGENT; GROWTH-INHIBITION; SOLID DISPERSION; DOWN-REGULATION; CELL-DEATH; KAPPA-B; APOPTOSIS;

D O I：

10.1016/j.biopha.2021.112043

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Despite its adverse effects, chemotherapy is generally used for the treatment of colorectal cancer (CRC). Development of supplement preparations targeting cancer stem cells (CSCs) that cause distant metastasis and drug resistance is required. Although curcumin is known to have anti-tumor, hepatoprotective, and hypoglycemic-like actions, its low water solubility, oral absorption, and bioavailability impede its therapeutic uses. Patient-derived organoid cultures can recapitulate heterogeneity, epithelial structures, and molecular imprints of their parental tissues. In the present study, anti-carcinogenic properties of amorphous curcumin (AC), a compound with improved solubility and bioavailability, were evaluated against human CRC organoids. Treatment with AC inhibited the cell viability of CRC organoids in a concentration-dependent manner. AC arrested the cell cycle of CRC organoids and induced apoptosis. AC inhibited phosphorylation of ERK. Expression of downstream signals of ERK, namely c-MYC and cyclin-D1, were inhibited. Expressions of CSC markers, CD44, LGR5, and CD133, were declined in the AC-treated CRC organoids. The combinational treatment of CRC organoids with AC and anti-cancer drugs, oxaliplatin, 5-FU, or irinotecan showed a synergistic activity. In vivo, AC decreased the tumor growth of CRC organoids in mice with the induction of necrotic lesions. In conclusion, AC diminished the cell viability of CRC organoids through the inhibition of proliferation-related signals and CSC marker expression in addition to arresting the cell cycle. Collectively, these data suggest the value of AC as a promising supplement that could be used in combination with anti-cancer drugs to prevent the recurrence and metastasis of CRC.

引用

页数：12

共 65 条

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