Growth suppression of human colorectal cancer cells with mutated KRAS by 3-deaza-cytarabine in 3d floating culture

Hao Luo; Kensuke Nishi; Shuhei Ishikura; Anthony Swain; Naoyuki Morishige; Ryo Yazaki; Takashi Ohshima; Senji Shirasawa; Toshiyuki Tsunoda

doi:10.21873/anticanres.12721

Growth suppression of human colorectal cancer cells with mutated KRAS by 3-deaza-cytarabine in 3d floating culture

Hao Luo, Kensuke Nishi, Shuhei Ishikura, Anthony Swain, Naoyuki Morishige, Ryo Yazaki, Takashi Ohshima, Senji Shirasawa, Toshiyuki Tsunoda

Chemo-Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

Original language	English
Pages (from-to)	4247-4256
Number of pages	10
Journal	Anticancer research
Volume	38
Issue number	7
DOIs	https://doi.org/10.21873/anticanres.12721
Publication status	Published - Jul 2018

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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10.21873/anticanres.12721

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@article{8d5320eacffa4741842e2b1a9e9c700f,

title = "Growth suppression of human colorectal cancer cells with mutated KRAS by 3-deaza-cytarabine in 3d floating culture",

abstract = "Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.",

author = "Hao Luo and Kensuke Nishi and Shuhei Ishikura and Anthony Swain and Naoyuki Morishige and Ryo Yazaki and Takashi Ohshima and Senji Shirasawa and Toshiyuki Tsunoda",

note = "Funding Information: The Authors thank Takami Danno, Yuriko Isoyama and Yumiko Hirose for their technical assistance. This study was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Publisher Copyright: {\textcopyright} 2018 International Institute of Anticancer Research. All rights reserved.",

year = "2018",

month = jul,

doi = "10.21873/anticanres.12721",

language = "English",

volume = "38",

pages = "4247--4256",

journal = "Anticancer research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "7",

}

TY - JOUR

T1 - Growth suppression of human colorectal cancer cells with mutated KRAS by 3-deaza-cytarabine in 3d floating culture

AU - Luo, Hao

AU - Nishi, Kensuke

AU - Ishikura, Shuhei

AU - Swain, Anthony

AU - Morishige, Naoyuki

AU - Yazaki, Ryo

AU - Ohshima, Takashi

AU - Shirasawa, Senji

AU - Tsunoda, Toshiyuki

N1 - Funding Information: The Authors thank Takami Danno, Yuriko Isoyama and Yumiko Hirose for their technical assistance. This study was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Publisher Copyright: © 2018 International Institute of Anticancer Research. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

AB - Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

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DO - 10.21873/anticanres.12721

M3 - Article

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SN - 0250-7005

VL - 38

SP - 4247

EP - 4256

JO - Anticancer research

JF - Anticancer research

IS - 7

ER -

Growth suppression of human colorectal cancer cells with mutated KRAS by 3-deaza-cytarabine in 3d floating culture

Abstract

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