Mitochondrial DNA determines the cellular response to cancer therapeutic agents

Keshav K. Singh, James Russell, Barbara Sigala, Yonggong Zhang, Jerry Williams, Kylie F. Keshav

Research output: Contribution to journalArticle

Abstract

Mutations in the mitochondrial genome leading to mitochondrial dysfunction have been reported in a variety of cancers. However, the potential implication of these findings in the cellular response to cancer therapeutic agents is unclear. To examine the importance of mitochondrial DNA (mitDNA) encoded functions in cancer therapeutic response, we determined the clonegenic survival of HSL2 (Rho+, HeLa subline), and its derivative cell line lacking mitDNA (Rho0) after exposure to different anticancer agents. We found that isogenic Rho0 cells lacking mitDNA were extremely resistant to adriamycin and photodynamic therapay (PDT) induced cell death, whereas the Rho+ cell line was sensitive. However, there was no measurable difference in the responses of these cell lines to either alkylating agent or γ-radiation. We show that the development of resistance to adriamycin was not due to changes in apoptotic cell death, cell cycle response or to the uptake of adriamycin in isogenic Rho0 cells. We also demonstrate that exposure of HeLa cells to adriamycin leads to mutations in mitDNA. These studies provide direct evidence that mitDNA plays an important role in cellular sensitivity to cancer therapeutic agents.

Original languageEnglish (US)
Pages (from-to)6641-6646
Number of pages6
JournalOncogene
Volume18
Issue number48
StatePublished - Nov 18 1999

Fingerprint

Mitochondrial DNA
Doxorubicin
Neoplasms
Cell Line
Cell Death
Therapeutics
Mutation
Mitochondrial Genome
Alkylating Agents
HeLa Cells
Antineoplastic Agents
Cell Cycle
Radiation

Keywords

  • Adriamycin
  • Cell death
  • Mitochondria
  • Mitochondrial DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Singh, K. K., Russell, J., Sigala, B., Zhang, Y., Williams, J., & Keshav, K. F. (1999). Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene, 18(48), 6641-6646.

Mitochondrial DNA determines the cellular response to cancer therapeutic agents. / Singh, Keshav K.; Russell, James; Sigala, Barbara; Zhang, Yonggong; Williams, Jerry; Keshav, Kylie F.

In: Oncogene, Vol. 18, No. 48, 18.11.1999, p. 6641-6646.

Research output: Contribution to journalArticle

Singh, KK, Russell, J, Sigala, B, Zhang, Y, Williams, J & Keshav, KF 1999, 'Mitochondrial DNA determines the cellular response to cancer therapeutic agents', Oncogene, vol. 18, no. 48, pp. 6641-6646.
Singh KK, Russell J, Sigala B, Zhang Y, Williams J, Keshav KF. Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene. 1999 Nov 18;18(48):6641-6646.
Singh, Keshav K. ; Russell, James ; Sigala, Barbara ; Zhang, Yonggong ; Williams, Jerry ; Keshav, Kylie F. / Mitochondrial DNA determines the cellular response to cancer therapeutic agents. In: Oncogene. 1999 ; Vol. 18, No. 48. pp. 6641-6646.
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