Rapamycin Enhances Apoptosis and Increases Sensitivity to Cisplatin in Vitro

Yufang Shi, Andrea Frankel, Gordon Mills, Laszlo G. Radvanyi, Richard G. Miller, Linda Z. Penn

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Apoptosis can be regulated in a number of different systems by the actions of cytokines. Rapamycin has been shown to exert its effects on growth factor-induced cell proliferation, at least in part, by blocking the activation of the p70 S6 kinase and thus preventing the downstream signaling process, such as the activation of the members of the cdk family. To determine whether this pathway plays a role in the regulation of apoptosis, we assessed the effect of rapamycin on apoptosis induced by interleukin 2 deprivation in murine T-cell lines, by T-cell receptor ligation in a murine T-cell hybridoma, by enforced c-myc expression in murine fibroblasts, and by corticosteroids in murine T-lymphoma cell lines. Although rapamycin did not induce apoptosis on its own, rapamycin augmented apoptosis in each of the cell lines used as indicated by increased genomic DNA fragmentation, decreased cell viability, and characteristic apoptotic changes in morphology. These results suggest that a signal transduction pathway(s) inhibited by rapamycin plays an important role in the susceptibility of cells to apoptosis. Many chemotherapeutic agents kill cancer cells through the induction of apoptosis. Strikingly, rapamycin increased the ability of the alkylating agent, cisplatin, to induce apoptosis in the human promyelocyte leukemia cell line HL-60 and the human ovarian cancer cell line SKOV3. These data suggest that a signal transduction pathway, likely related to p70 S6 kinase, inhibited by rapamycin may be an important component of the pathway which prevents cell death in many cell lineages and also indicate that rapamycin has the potential to augment the efficacy of selected anticancer therapies.

Original languageEnglish (US)
Pages (from-to)1982-1988
Number of pages7
JournalCancer Research
Volume55
Issue number9
StatePublished - May 1 1995
Externally publishedYes

Fingerprint

Sirolimus
Cisplatin
Apoptosis
Cell Line
70-kDa Ribosomal Protein S6 Kinases
Signal Transduction
T-Lymphocytes
Granulocyte Precursor Cells
Aptitude
In Vitro Techniques
Alkylating Agents
Hybridomas
Cell Lineage
DNA Fragmentation
T-Cell Antigen Receptor
Ovarian Neoplasms
Interleukin-2
Ligation
Lymphoma
Cell Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Shi, Y., Frankel, A., Mills, G., Radvanyi, L. G., Miller, R. G., & Penn, L. Z. (1995). Rapamycin Enhances Apoptosis and Increases Sensitivity to Cisplatin in Vitro. Cancer Research, 55(9), 1982-1988.

Rapamycin Enhances Apoptosis and Increases Sensitivity to Cisplatin in Vitro. / Shi, Yufang; Frankel, Andrea; Mills, Gordon; Radvanyi, Laszlo G.; Miller, Richard G.; Penn, Linda Z.

In: Cancer Research, Vol. 55, No. 9, 01.05.1995, p. 1982-1988.

Research output: Contribution to journalArticle

Shi, Y, Frankel, A, Mills, G, Radvanyi, LG, Miller, RG & Penn, LZ 1995, 'Rapamycin Enhances Apoptosis and Increases Sensitivity to Cisplatin in Vitro', Cancer Research, vol. 55, no. 9, pp. 1982-1988.
Shi Y, Frankel A, Mills G, Radvanyi LG, Miller RG, Penn LZ. Rapamycin Enhances Apoptosis and Increases Sensitivity to Cisplatin in Vitro. Cancer Research. 1995 May 1;55(9):1982-1988.
Shi, Yufang ; Frankel, Andrea ; Mills, Gordon ; Radvanyi, Laszlo G. ; Miller, Richard G. ; Penn, Linda Z. / Rapamycin Enhances Apoptosis and Increases Sensitivity to Cisplatin in Vitro. In: Cancer Research. 1995 ; Vol. 55, No. 9. pp. 1982-1988.
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