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Investigational New Drugs

, Volume 31, Issue 2, pp 333–344 | Cite as

Enhanced killing of cervical cancer cells by combinations of methyl jasmonate with cisplatin, X or alpha radiation

  • Elad Milrot
  • Anna Jackman
  • Eliezer Flescher
  • Pinhas Gonen
  • Itzhak Kelson
  • Yona Keisari
  • Levana ShermanEmail author
PRECLINICAL STUDIES

Summary

Current therapies for treatment of advanced cervical cancer involve the use of cisplatin, often in combination with radiotherapy. These treatments do not lead to a high survival rate and furthermore, serious side effects are dose-limiting factors. Methyl jasmonate (MJ) was recently identified as potent and selective cytotoxic agent towards cervical cancer cells. In the present study we evaluated the effectiveness of combined treatments of MJ with cisplatin or X-irradiation on a variety of cervical cancer cells including SiHa, CaSki, HeLa and C33A. Cytotoxicity of alpha particles, emitted from 224Ra atoms, was also evaluated as a single agent and in combination with MJ. Cooperation between MJ and cisplatin in reducing cell viability (XTT assays) and survival (clonogenicity assays) was exhibited towards several cancer cell lines at a range of combination doses. MJ effectively cooperated also with X-ray irradiation, significantly lowering the radiation doses required to inhibit cell survival (ID50) of all tested cells lines. We show for the first time, that alpha irradiation selectively reduced cell viability and survival of cervical cancer cells. Lower doses of α irradiation were required as compared to X-irradiation to inhibit cell survival. Cooperation with MJ was demonstrated in part of the cancer cell lines. In conclusion, our studies point to α irradiation and MJ, novel anticancer agents, as potent candidates for treatment of cervical cancer, in single agent regiments and in combination. MJ can be added also to conventional X-ray and cisplatin therapies to increase their cytotoxic effect while lowering the effective dose.

Keywords

Cervical cancer Therapies for cervical cancer Methyl jasmonate Cisplatin X-ray radiation Alpha radiation Combination treatments 

Notes

Acknowledgments

This research was supported by a research grant from the Chief Scientist’s Office, Ministry of Health, Israel (grant 3–3066) awarded to LS and in part by a grant from the Bernard Jacobson Fund for Cancer Research, Tel-Aviv University, awarded to LS, and a grant from the Israel Cancer Association, awarded to YK.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Elad Milrot
    • 1
  • Anna Jackman
    • 1
  • Eliezer Flescher
    • 1
  • Pinhas Gonen
    • 1
  • Itzhak Kelson
    • 2
  • Yona Keisari
    • 1
  • Levana Sherman
    • 1
    Email author
  1. 1.Department of Clinical Microbiology and Immunology, Sackler School of MedicineTel-Aviv UniversityTel-AvivIsrael
  2. 2.School of Physics and Astronomy, Raymond and Beverly Sackler School of Exact SciencesTel-Aviv UniversityTel-AvivIsrael

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