Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma

Abstract In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by co...

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Autores principales:	T. Mantso, S. Vasileiadis, I. Anestopoulos, G. P. Voulgaridou, E. Lampri, S. Botaitis, E. N. Kontomanolis, C. Simopoulos, G. Goussetis, R. Franco, K. Chlichlia, A. Pappa, M. I. Panayiotidis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a30c6cdadc354acd984bd426de336f4b
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spelling	oai:doaj.org-article:a30c6cdadc354acd984bd426de336f4b2021-12-02T16:08:15ZHyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma10.1038/s41598-018-29018-02045-2322https://doaj.org/article/a30c6cdadc354acd984bd426de336f4b2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29018-0https://doaj.org/toc/2045-2322Abstract In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia’s therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction.T. MantsoS. VasileiadisI. AnestopoulosG. P. VoulgaridouE. LampriS. BotaitisE. N. KontomanolisC. SimopoulosG. GoussetisR. FrancoK. ChlichliaA. PappaM. I. PanayiotidisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q T. Mantso S. Vasileiadis I. Anestopoulos G. P. Voulgaridou E. Lampri S. Botaitis E. N. Kontomanolis C. Simopoulos G. Goussetis R. Franco K. Chlichlia A. Pappa M. I. Panayiotidis Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
description	Abstract In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia’s therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction.
format	article
author	T. Mantso S. Vasileiadis I. Anestopoulos G. P. Voulgaridou E. Lampri S. Botaitis E. N. Kontomanolis C. Simopoulos G. Goussetis R. Franco K. Chlichlia A. Pappa M. I. Panayiotidis
author_facet	T. Mantso S. Vasileiadis I. Anestopoulos G. P. Voulgaridou E. Lampri S. Botaitis E. N. Kontomanolis C. Simopoulos G. Goussetis R. Franco K. Chlichlia A. Pappa M. I. Panayiotidis
author_sort	T. Mantso
title	Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
title_short	Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
title_full	Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
title_fullStr	Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
title_full_unstemmed	Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
title_sort	hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a30c6cdadc354acd984bd426de336f4b
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Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma

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