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 Sherman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)333-344
Number of pages12
JournalInvestigational New Drugs
Volume31
Issue number2
DOIs
StatePublished - Apr 2013

Funding

FundersFunder number
Bernard Jacobson Fund for Cancer Research
Chief Scientist Office
Israel Cancer Association
Tel Aviv University
Ministry of Health, State of Israel3– 3066

    Keywords

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

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