In vitro Effect of Hyperthermia on Chemoenhancement and Uptake of Cisplatin in Human Pharyngeal Carcinoma KB Cells

Abstract

The purpose of this study was to assess the efficacy of hyperthermia (42 or 44 °C) as a modifier of cis-diamminedichloro-platinum (II) (CDDP) cytotoxicity and platinum incorporation in human pharyngeal carcinoma KB cells. To maximize the interactive effect, we examined the time sequence of high (above 43 °C) or low (below 43 °C) hyperthermia and CDDP. Within the dose range of CDDP studied, there was a marked synergism between the effects of heating at 44 °C and subsequent CDDP exposure for 5 h. Pretreatment at 44 °C for 30 min or at 42 ° C for 4 h enhanced CDDP cytotoxicity more than posttreatment at 44 °C for 30 min or at 42 °C for 4h. However, the chemoenhancement ratio of pretreatment at 44 ° C for 30 min was higher than that of pretreatment at 42 ° C for 4 h, although the thermal isotoxic dose decreased the cell count to 60% under both conditions. There was a significant increase in CDDP uptake after hyperthermia at 44 °C. These results indicate that high hyperthermia effectively enhances subsequent CDDP cytotoxicity in human pharyngeal carcinoma KB cells.

Uptake of antitumor platinum(II)-complexes by cancer cells, assayed by inductively coupled plasma mass spectrometry (ICP-MS)

“…To the best of our knowledge, most of the uptake studies have been carried out with protocols far from real pharmacological conditions (i.e. drug concentration higher than the IC 50 value and very short treatment periods) [7][8][9][10][13][14][15][16][26][27][28][29][30][31][32][33][34][35][36][37].…”

“…In order to utilise all the spread data in the literature [7,9,13,15,16,[26][27][28][32][33][34][35], we assume that 1 million of cells is roughly equivalent to 1 mg protein [39].…”

“…Indeed, the cisplatin uptake is directly proportional to its concentration, is not inhibited by structural analogues, and is not saturable [12]. Hyperthermia, as well as radiation or chemical stimuli, cause higher uptake rate, probably due to an increased permeability of the cell membrane [13,14]. An alternative Journal of Inorganic Biochemistry 98 (2004) 73-78 www.elsevier.com/locate/jinorgbio JOURNAL OF Inorganic Biochemistry transport system mediated by membrane proteins seems, at least in part, operative: a variety of pharmacological agents, that do not alter the permeability of the membrane, inhibit cisplatin uptake [2,3,12,15].…”

The influence of temperature on antiproliferative effects, cellular uptake and DNA platination of the clinically employed Pt(II)-drugs

“…The overall effect of heat and Pt(II)-drugs can be additive or synergistic, depending on the drug, the cell line, the temperature, the treatment time and scheduling procedure [21,22,26,[28][29][30][31][32][33][34]. At a first glance, cisplatin shows the greatest enhancement in cell killing with heat among platinum(II) complexes [25,28,31,32].…”

Cytotoxic Effect of Hyperthermia and Chemotherapy with Platinum Salt on Ovarian Cancer Cells: Results of an in vitro Study

“…When carboplatin was used with temperatures from 40.5 to 41.8°C on a human acute lymphoblastic cell line, the maximal efficacy was observed when heat was delivered during or immediately before carboplatin, whereas the efficacy was reduced when heat preceded carboplatin by more than 1 h and disappeared when heat was delivered after drug treatment [36]. The same conclusions were reached when cisplatin was used on various malignant cell lines [37,38,39]. …”