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

Scientific Reports
T MantsoM I Panayiotidis

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 sign...Continue Reading

References

May 1, 1978·International Journal of Radiation Oncology, Biology, Physics·R E Durand
May 9, 1998·Neurosurgery·T FuseK Yamada
Dec 29, 2000·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·D KobayashiY Niitsu
Jul 6, 2002·Critical Reviews in Oncology/hematology·Bert HildebrandtHanno Riess
Aug 16, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J van der Zee
Apr 9, 2004·The Journal of Biological Chemistry·Kezhong Zhang, Randal J Kaufman
May 12, 2005·Journal of Cellular Physiology·Ahmed Bettaieb, Diana A Averill-Bates
Jan 7, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sae Hee KoDouglas S Tyler
Sep 2, 2006·Biochemical and Biophysical Research Communications·Patrycja Nowak-SliwinskaKrystyna Urbanska
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Jun 19, 2007·Cellular and Molecular Life Sciences : CMLS·R S Milleron, S B Bratton
Nov 9, 2007·The Journal of Investigative Dermatology·Yiqun G ShellmanDavid A Norris
Nov 10, 2007·Science·Jonathan H LinPeter Walter
Dec 19, 2007·The Journal of Biological Chemistry·Jagadish C GhoshDario C Altieri
Sep 16, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rolf D Issels
Nov 27, 2008·The American Journal of Surgical Pathology·Janis M TaubeWilliam H Westra
Jan 13, 2009·PloS One·Jonathan H LinPeter Walter
Jan 17, 2009·Nature Reviews. Microbiology·Tessa BergsbakenBrad T Cookson
Jul 16, 2010·Nature Reviews. Molecular Cell Biology·Malin AkerfeltLea Sistonen
Sep 23, 2010·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Hua ShenYong-Qian Shu
Oct 15, 2010·The FEBS Journal·Johanna K Björk, Lea Sistonen
Oct 28, 2010·The Journal of Biological Chemistry·Shary N SheltonJohn D Robertson
Aug 13, 2011·Pigment Cell & Melanoma Research·Andrzej SlominskiJohn Pawelek
Nov 15, 2011·Apoptosis : an International Journal on Programmed Cell Death·Yukihiro FurusawaTakashi Kondo
Jan 3, 2012·Journal of Biochemistry·Hideki Nishitoh
Apr 26, 2012·PloS One·Mónica Pereira GarciaMaria Helena Fernandes
May 5, 2012·Journal of Translational Medicine·Paolo A AsciertoNicola Mozzillo
Jan 22, 2013·Nanoscale·Jessica MorlierasOlivier Tillement
Feb 20, 2013·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Ana PortelaJosé Cavalheiro
Aug 22, 2013·Journal of the European Academy of Dermatology and Venereology : JEADV·M ArnoldE de Vries
Sep 28, 2014·Biochimica Et Biophysica Acta·Ahmed Bettaieb, Diana A Averill-Bates

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Citations

Jan 5, 2019·Journal of Biomaterials Science. Polymer Edition·Paula Christina Mattos Dos SantosPedro Henrique Hermes de Araújo
Mar 25, 2019·Nature Communications·Zhenglong Zhou, Chaz Firestone
Apr 27, 2019·Frontiers in Chemistry·Jeremy B VinesHansoo Park
May 28, 2020·Frontiers in Chemistry·Ivan V KrylovEvgeny V Khaydukov
Aug 23, 2020·Nature Protocols·Chuan YanDavid M Langenau
Oct 28, 2019·Scientific Reports·Rosa OrlacchioMaxim Zhadobov
Jun 20, 2020·Journal of Biomaterials Science. Polymer Edition·Paula Christina Mattos Dos SantosPedro Henrique Hermes de Araújo
Apr 10, 2019·Polymers·Jeremy B VinesHansoo Park
May 15, 2021·Scientific Reports·Wan Fatin Amira Wan Mohd ZawawiK Jemon
Jun 3, 2021·International Journal of Molecular Sciences·Mercedes QuintanaJosé Quintana

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Methods Mentioned

BETA
PCR
PMAIP1
protein folding
Assay
electrophoresis
protein assay

Software Mentioned

PRISM
SPSS
Excel
Office
DataAssist

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