Azatyrosinamides: Novel RAS-related anticancer agents

Chun Li Wang, On Lee, Chiu Fen Huang, Eric I Chian Li, Che Ming Teng, Shiow Lin Pan, Jang Feng Lian, Feng Shou Chang, Jing Ping Liou, Hui Po Wang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: We previously reported on the design and synthesis of novel azatyrosinamide derivatives selective for ras-transformed NIH3T3 cells and with improved toxicity over azatyrosine. This study was aimed at investigating the mechanism of action and the antitumour activity of these compounds in ras-transformed cells. Materials and Methods: Nine azatyrosinamides were previously screened for anticancer activity in both wild-type and ras-transformed NIH3T3 cells; the most active compounds were further tested in vitro and in vivo. Results: HPW98-1 and HPW98-2 induced formation of apoptotic bodies in ras-transformed NIH3T3 cells in vitro and inhibited anchorage-independent growth. Excess tyrosine reduced the cytotoxic effect of azatyrosine, but not of HPW98-1 and HPW98-2. HPW98-1 reduced vascular endothelial growth factor-mediated angiogenesis in a Matrigel plug assay and attenuated growth of a ras-transformed NIH3T3 xenograft and a human SW620 xenograft. Conclusion: Our results support the continued study of HPW98-1 for its potential use in the treatment of RAS-related cancers.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalAnticancer Research
Volume33
Issue number2
Publication statusPublished - Feb 2013

Fingerprint

Antineoplastic Agents
Heterografts
Second Primary Neoplasms
Growth
Vascular Endothelial Growth Factor A
Tyrosine
In Vitro Techniques
beta-(5-hydroxy-2-pyridyl)alanine

Keywords

  • Angiogenesis
  • Antitumour agent
  • Azatyrosinamides
  • NIH3T3
  • Ras
  • SW620 human colon xenograft

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wang, C. L., Lee, O., Huang, C. F., Li, E. I. C., Teng, C. M., Pan, S. L., ... Wang, H. P. (2013). Azatyrosinamides: Novel RAS-related anticancer agents. Anticancer Research, 33(2), 425-432.

Azatyrosinamides : Novel RAS-related anticancer agents. / Wang, Chun Li; Lee, On; Huang, Chiu Fen; Li, Eric I Chian; Teng, Che Ming; Pan, Shiow Lin; Lian, Jang Feng; Chang, Feng Shou; Liou, Jing Ping; Wang, Hui Po.

In: Anticancer Research, Vol. 33, No. 2, 02.2013, p. 425-432.

Research output: Contribution to journalArticle

Wang, CL, Lee, O, Huang, CF, Li, EIC, Teng, CM, Pan, SL, Lian, JF, Chang, FS, Liou, JP & Wang, HP 2013, 'Azatyrosinamides: Novel RAS-related anticancer agents', Anticancer Research, vol. 33, no. 2, pp. 425-432.
Wang CL, Lee O, Huang CF, Li EIC, Teng CM, Pan SL et al. Azatyrosinamides: Novel RAS-related anticancer agents. Anticancer Research. 2013 Feb;33(2):425-432.
Wang, Chun Li ; Lee, On ; Huang, Chiu Fen ; Li, Eric I Chian ; Teng, Che Ming ; Pan, Shiow Lin ; Lian, Jang Feng ; Chang, Feng Shou ; Liou, Jing Ping ; Wang, Hui Po. / Azatyrosinamides : Novel RAS-related anticancer agents. In: Anticancer Research. 2013 ; Vol. 33, No. 2. pp. 425-432.
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