Cytotoxicity studies of combination of proteasome inhibitor Velcade and hyperthermia

Dinara Baiskhanova, Timur Saliev, Dinara Begimbetova, Loreto B. Feril, Xeniya Merinyanu, Katsuro Tachibana

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

One of perspective methods of cancer treatment is the induction of apoptosis (‘programmed cell death’) in malignant cells. The
apoptosis can be stimulated by various factors: biological, chemical and physical. We investigated cytotoxic effect of combination
of pharmacological apoptosis modulator Velcade (Janssen-Cilag Pty Ltd) and hypethermia. The cytotoxicity was studied for 5
concentrations of Velcade (1, 2, 3, 4 and 5 ng/ml), three types of temperature (40, 42 and 44°C), and two types of cancer cells (human
melanoma C-32 and human monocytic leukaemia U937 lines). The results demonstrated that Velcade in all 5 concentrations was
able of suppress the viability of U937 cells. The decrease in cell survival rate was in a direct correlation with the increase of drug’s
concentration. The maximal level of dead cells was detected for 40°C for all concentrations of Velcade. However, the acquired data
showed that the augmentation of temperature up to 42°C and 44°C resulted in the rise of number of viable cells. These findings
indicate that high temperatures have a cyto-protective effect. The possible mechanism may lay in the ability of mild hyperthermia to
promote cell growth. The second feasible explanation is a negative impact of high temperature on Velcade’s pharmacodynamics. The
data of cytotoxicity studies of C-32 cells showed a similar picture. The elevation of temperature led to the decrease of cells viability.
Notably, the highest temperature (44°C) had a cyto-protective effect too. In conclusion, our findings indicate that combination of
apoptosis modulator Velcade and mild hypethermia can be effectively employed for the elimination of cancer cells.
Original languageEnglish
Title of host publicationCytotoxicity studies of combination of proteasome inhibitor Velcade and hyperthermia
Place of PublicationCologne, Germany
Number of pages1
DOIs
Publication statusPublished - 2016

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