Cited by 1,080Redox biology and oxidative stressBioactive Compounds and Antitumor AgentsCell death mechanisms and regulation

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Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate

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Trachootham, Dunyaporn, Zhou, Yan, Zhang, Hui, Demizu, Yusuke, Chen, Zhao, Pelicano, Helene, Chiao, Paul J., Achanta, Geetha, Arlinghaus, Ralph B., Liu, Jinsong, Huang, Peng·2006·Cancer Cell

DOI 10.1016/j.ccr.2006.08.009

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Abstract

Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic instability, and their increase in cancer cells is often viewed as an adverse event. Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using beta-phenylethyl isothiocyanate (PEITC). Oncogenic transformation of ovarian epithelial cells with H-Ras(V12) or expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and renders the malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output. Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.

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Authors: Trachootham, D., Zhou, Y., Zhang, H., Demizu, Y., Chen, Z., Pelicano, H., Chiao, P. J., Achanta, G., Arlinghaus, R. B., Liu, J., & Huang, P.
Affiliations: Thammasat University (TH)
The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Huang, Peng
ORCID: Trachootham, Dunyaporn
Zhou, Yan
Zhang, Hui
Demizu, Yusuke
Chiao, Paul J.
Liu, Jinsong
Huang, Peng
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2006-09
Volume: 10
Issue: 3
Pages: 241-252
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2006.08.009
OpenAlex: W1993238109
Cited by: 1,080
References: 43
Citations by year: 2026: 13 · 2025: 26 · 2024: 36 · 2023: 40 · 2022: 59 · 2021: 54 · 2020: 50 · 2019: 58 · 2018: 58 · 2017: 68 · 2016: 83 · 2015: 59 · 2014: 83 · 2013: 65 · 2012: 73
FWCI: 16.57
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2511 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (CA-16 672)
National Cancer Institute (CA-16672, CA085563, R01CA109041, CA109041, R01CA085563, R01CA100428, CA100428, P30CA016672)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: reactive oxygen species, selective cytotoxicity, oncogenic transformation, H-Ras V12, BCR-ABL, glutathione antioxidant system, oxidative stress, ovarian epithelial cells, hematopoietic cells, cancer cell death, cancer therapy
MeSH terms: Animals, Antioxidants, Cell Line, Cell Transformation, Neoplastic, Glutathione, Humans, Neoplasms, Oncogene Protein p21(ras), Survival Rate, Fusion Proteins, bcr-abl, Cell Death, Reactive Oxygen Species, Isothiocyanates, Xenograft Model Antitumor Assays, Mice

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Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate

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