title: Enhanced killing of cervical cancer cells by combinations of methyl jasmonate with cisplatin, X or alpha radiation.
abstract: 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 (224)Ra 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.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Milrot
authors.forename: Anna
authors.initials: A
authors.lastname: Jackman
authors.forename: Eliezer
authors.initials: E
authors.lastname: Flescher
authors.forename: Pinhas
authors.initials: P
authors.lastname: Gonen
authors.forename: Itzhak
authors.initials: I
authors.lastname: Kelson
authors.forename: Yona
authors.initials: Y
authors.lastname: Keisari
authors.forename: Levana
authors.initials: L
authors.lastname: Sherman
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000512:Alpha Particles; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003517:Cyclopentanes / Q000494:pharmacology*; D005260:Female; D005720:Gamma Rays; D006801:Humans; D054883:Oxylipins / Q000494:pharmacology*; D010937:Plant Growth Regulators / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy
chemical_list: D000085:Acetates; D003517:Cyclopentanes; D054883:Oxylipins; D010937:Plant Growth Regulators; D011838:Radiation-Sensitizing Agents; C072239:methyl jasmonate; D002945:Cisplatin