Metakaryotic cancer stem cells are constitutively resistant to X-rays and chemotherapeutic agents, but sensitive to many common drugs

Elena V. Gostjeva, Vera V. Koledova, Liyuan Bai, Kailin C. Duan, Tushar Kamath, Meghan Nelson, Parul Agnihotri, Deborah J. Moshinski, Li Ping Wu, Lawrence Zukerberg, Daniel C. Chung, Susan Tsai, Douglas B. Evans, Aoy Tomita-Mitchell, Michael Mitchell, William G. Thilly

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

After radio- and chemo-therapy, human tumors display many dead eukaryotic cells with pyknotic nuclei. But amitotic metakaryotic cells with hollow, bell-shaped nuclei appear unaffected as expected of treatment-resistant cancer stem cells. These same phenomena may be observed in vitro using any of many tumor- or metastasis-derived cell lines, for which their immortality is conferred by the presence of amitotic, metakaryotic cancer stem cells. About 5% of human colonic adenocarcinoma-derived HT-29 cells in exponential growth are immortal metakaryotic stem cells that increase by symmetric amitoses and continuously create mortal mitotic eukaryotic cells by asymmetric amitoses. Two assays for agents/conditions lethal to metakaryotic stem cells have been devised: (1) microscopic recognition of necrotic metakaryotic nuclei; and (2) survival of cells forming large immortal colonies visibly containing metakaryotic stem cells in vitro. X-rays and chemotherapeutic agents (i.e., alkylating agents, antimetabolites, and mitocides) kill eukaryotic cells, but not metakaryotic cells, at doses commonly used in cancer therapy. In contradistinction, multiple classes of common drugs are preferentially cytotoxic to metakaryotic stem cells including NSAIDS, antibiotics, and drugs used to treat diabetes or hypertension. Given lesion penetration and treatments of sufficient duration, regimens using multiple metakaryocidal drugs offer means to treat and prevent cancers.

Original languageEnglish (US)
Title of host publicationToxicology, Survival and Health Hazards of Combustion Products
PublisherRoyal Society of Chemistry
Pages196-249
Number of pages54
Volume2016-January
Edition29
DOIs
StatePublished - 2016
Externally publishedYes

Publication series

NameIssues in Toxicology
Number29
Volume2016-January
ISSN (Print)17577179
ISSN (Electronic)17577187

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Metakaryotic cancer stem cells are constitutively resistant to X-rays and chemotherapeutic agents, but sensitive to many common drugs'. Together they form a unique fingerprint.

  • Cite this

    Gostjeva, E. V., Koledova, V. V., Bai, L., Duan, K. C., Kamath, T., Nelson, M., Agnihotri, P., Moshinski, D. J., Ping Wu, L., Zukerberg, L., Chung, D. C., Tsai, S., Evans, D. B., Tomita-Mitchell, A., Mitchell, M., & Thilly, W. G. (2016). Metakaryotic cancer stem cells are constitutively resistant to X-rays and chemotherapeutic agents, but sensitive to many common drugs. In Toxicology, Survival and Health Hazards of Combustion Products (29 ed., Vol. 2016-January, pp. 196-249). (Issues in Toxicology; Vol. 2016-January, No. 29). Royal Society of Chemistry. https://doi.org/10.1039/9781782626787-00196