Disruption of cancer cell replication by alternating electric fields.
Low-intensity, intermediate-frequency (100-300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3-6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.
Kirson
Eilon D
ED
Department of Biomedical Engineering, NovoCure Ltd., Haifa, Israel.
Gurvich
Zoya
Z
Schneiderman
Rosa
R
Dekel
Erez
E
Itzhaki
Aviran
A
Wasserman
Yoram
Y
Schatzberger
Rachel
R
Palti
Yoram
Y
D000818:Animals; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D004599:Electric Stimulation Therapy; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D051381:Rats