Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate
Open accessAbstract
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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Compounds that raise ROS levels can effectively and selectively kill a variety of tumor cell lines.
“Indeed, this seems to be the case as compounds that raise ROS levels can effectively and selectively kill a variety of tumor cell lines 31, 74, 75.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [75]
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Cancer Cell MetabolismPreprint
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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
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 10
- Issue
- 3
- Pages
- 241-252
- ISSN
- 1535-6108 (ISSN-L)
- 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
- 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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