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

Research output: Contribution to journalArticle

1 Citation (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 languageEnglish
Pages (from-to)4247-4256
Number of pages10
JournalAnticancer research
Volume38
Issue number7
DOIs
Publication statusPublished - Jul 2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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