Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3: in vitro studies

Abstract

Background The purpose of this study was to investigate the therapeutic efficacy of dextran-coated (Dex) La 0.7 Sr 0.3 MnO 3 (LSMO) nanoparticles-mediated hyperthermia at different temperatures (43°C, 45°C, and 47°C) based on cell killing potential and induction of heat shock proteins in a murine melanoma cell (B16F1) line. Methods LSMO nanoparticles were synthesized by a citrate-gel method and coated with dextran. B16F1 cells were exposed to the Dex-LSMO nanoparticles and heated using a radiofrequency generator. After heating, the morphology and topology of the cells were investigated by optical microscopy and atomic force microscopy. At 0 hours and 24 hours post heating, cells were harvested and viability was analyzed by the Trypan blue dye exclusion method. Apoptosis and DNA fragmentation were assessed by terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay and agarose gel electrophoresis, respectively. An enzyme-linked immunosorbent assay was used to quantify heat shock protein levels. Results Our data indicate that cell death and induction of heat shock proteins in melanoma cells increased in a time-dependent and temperature-dependent manner, particularly at temperatures higher than 43°C. The mode of cell death was found to be apoptotic, as evident by DNA fragmentation and TUNEL signal. A minimum temperature of 45°C was required to irreversibly alter cell morphology, significantly reduce cell viability, and result in 98% apoptosis. Repeated cycles of hyperthermia could induce higher levels of heat shock proteins (more favorable for antitumor activity) when compared with a single cycle. Conclusion Our findings indicate a potential use for Dex-LSMO-mediated hyperthermia in the treatment of melanoma and other types of cancer.

HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death

“…Haghniaz et al showed a minimum temperature of 45°C was required to decrease the viability of the melanoma cell line B16F [1]. Our study obtained consistent results by using temperatures lower than 45°C and showed these temperatures failed to eliminate B16 cells.…”

“…Hyperthermia is a procedure by which the temperature of a specific body part or the whole organism is elevated above the standard physiological temperature [ 1 ]. A temperature range of 42°C to 45°C is used therapeutically as a single agent or as an adjuvant to radiotherapy, chemotherapy or immunotherapy in the cancer treatment [ 2 , 3 ].…”

Ultrasound microbubble potentiated enhancement of hyperthermia-effect in tumours

“…Changes in the vasculature however appeared dependent on ultrasound pressure but largely invariant over the heating times studied. Several studies have confirmed time-dependent cellular effect using various in vivo and in vitro models but these have made use of USMB to perturb the vasculature in advance [37] [38].…”

“…Interestingly, HT range between 39–45°C has demonstrated enhanced blood flow followed by improved tissue oxygenation causing direct or indirect cell death leading vascular deterioration [44] [45]. The mode of cell death induced by HT is known to be time-and temperature-dependent [46] [37] [47]. Usually, temperature up to 47°C results in apoptotic cell death while increasing the temperature above 50°C exhibits necrosis as a result of tumour cells destruction [36].…”

Recurrent heat shock impairs the proliferation and differentiation of C2C12 myoblasts

“…While the acute or moderate HS can be managed physiologically by the endogenous defense systems, severe and/or continuous heat stress, accompanied by over-expression of certain heat shock proteins, overburdens the physiological maneuvers leading to ineffective defense, organ damage, and lethality (Dehbi et al 2010). For example, repeated cycles of hyperthermia were shown to dramatically increase HSP production when compared to a single, acute HS, resulting in enhanced apoptosis (Haghniaz et al 2015). Prolonged exposure to heat stress has been shown to increase the production of reactive oxygen species (ROS) in skeletal muscle (Azad et al 2010) that can enhance various deleterious consequences such as protein modifications, proteolysis, autophagy, and inflammation and affect skeletal muscle physiology (Montilla et al 2014;Dodd et al 2010;McClung et al 2010;Whidden et al 2010).…”