Hyperthermia and cytotoxic drugs. Possible use of lanthanum as a potentiator of hyperthermia

Abstract

Recent studies indicate that differences in membrane fluidity may account for differences of thermal sensitivity. This possibility was studied by using lanthanum, a trivalent cation which is known to displace calcium in a number of biological systems, to modify the structural framework of cell membranes and consequently their biological properties.

With Ehrlich ascites cells trypan blue exclusion uptake of ⁸⁶Rb, ⁴²K and ⁴⁵Ca, indicate an increase of plasma cell permeability by La³⁺. The reduction of ⁸⁶Rb and ⁴²K uptake by tumour cells with La³⁺ appears to be independent of temperature. The increase of ⁴⁵Ca²⁺ influx in the presence of lanthanum plus hyperthermia seems related to an important loss of cell viability. The enhancement of hyperthermia lethality by concentrations of lanthanum over 0.5 mM after 2 h at 44°C has been demonstrated using HeLa S3 cells using a standard cloning technique. In vivo experiments have been performed on C3H mice bearing rhabdomyosarcoma using ultrasound heating at 44-46°C. The results show a remarkable inhibition of tumour growth and a significant increase of the survival time after only one hyperthermia session of 30 min combined with one intratumoural injection of 1 mM lanthanum chloride.

Keywords::

• lanthanum
• potentiator
• hyperthermia
• cytotoxicity
• drugs