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Research ArticleExperimental Studies

Effectiveness of Hyperthermia as Monotherapy and Adjuvant Therapy Approaches Against an In Vitro Model of Colorectal Carcinoma

GEORGIOS PETRAKIS, THEODORA MANTSO, MICHAIL I. KOUKOURAKIS, MIHALIS I. PANAYIOTIDIS and SOTIRIS BOTAITIS
Anticancer Research May 2022, 42 (5) 2363-2374; DOI: https://doi.org/10.21873/anticanres.15715
GEORGIOS PETRAKIS
1Saint George Hospital, Chania, Greece;
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THEODORA MANTSO
2Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, U.K.;
3Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece;
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MICHAIL I. KOUKOURAKIS
4Department of Radiotherapy/Oncology, University Hospital, Democritus University of Thrace, School of Medicine, Alexandroupolis, Greece;
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MIHALIS I. PANAYIOTIDIS
2Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, U.K.;
5Department of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus;
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  • For correspondence: smpotait@med.duth.gr mihalisp@cing.ac.cy
SOTIRIS BOTAITIS
6Department of Surgery, University Hospital, Democritus University of Thrace, School of Medicine, Alexandroupolis, Greece
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  • For correspondence: smpotait@med.duth.gr mihalisp@cing.ac.cy
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Abstract

Background/Aim: Despite improvement in current therapies, the 5-year overall survival rate of colorectal carcinoma is still low especially in its metastatic form. On the other hand, hyperthermia has been utilized as a cancer treatment approach to improve overall therapeutic efficacy. In the present study, we have aimed to develop an optimized hyperthermic protocol against an in vitro model of human colon carcinoma, as a single and/or adjuvant treatment approach. Materials and Methods: We have utilized an in vitro model of human colorectal carcinoma consisting of colorectal carcinoma (HT29, CaCo2) and normal colon epithelial (CCD841CoN) cell lines. Cells were exposed to 45°C, over 120 min, in the presence or absence of chemotherapeutic (5-Fluorouracil, Capecitabine) and targeted (Bevacizumab, Cetuximab) drugs. Cell viability levels were determined by the Alamar-blue assay while determination of cell death, reactive oxygen species (ROS) production, mitochondrial membrane depolarization (ΔΨμ) levels and cell cycle progression were performed by flow cytometry. Results: CaCo2 and HT29 cells showed a differential response towards i) cell viability, ii) cell death, iii) ROS and ΔΨμ levels as well as iv) cell cycle distribution, in the presence of hyperthermia alone (monotherapy) or in combination with the above-mentioned drugs (adjuvant therapy). Finally, normal colon epithelial (CCD841CoN) cells remained minimally affected. Conclusion: We have developed an optimized experimental hyperthermic protocol, as a promising monotherapy and/or adjuvant therapy approach, with the capacity to potentiate chemotherapeutic as well as targeted drug-induced cytotoxicity against a model of colorectal carcinoma, to a variable degree.

Key Words:
  • Hyperthermia
  • colorectal carcinoma
  • cancer therapeutics
  • 5-fluorouracil
  • capecitabine
  • bevacizumab
  • cetuximab
  • Received February 23, 2022.
  • Revision received March 18, 2022.
  • Accepted March 24, 2022.
  • Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 42 (5)
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Effectiveness of Hyperthermia as Monotherapy and Adjuvant Therapy Approaches Against an In Vitro Model of Colorectal Carcinoma
GEORGIOS PETRAKIS, THEODORA MANTSO, MICHAIL I. KOUKOURAKIS, MIHALIS I. PANAYIOTIDIS, SOTIRIS BOTAITIS
Anticancer Research May 2022, 42 (5) 2363-2374; DOI: 10.21873/anticanres.15715

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Effectiveness of Hyperthermia as Monotherapy and Adjuvant Therapy Approaches Against an In Vitro Model of Colorectal Carcinoma
GEORGIOS PETRAKIS, THEODORA MANTSO, MICHAIL I. KOUKOURAKIS, MIHALIS I. PANAYIOTIDIS, SOTIRIS BOTAITIS
Anticancer Research May 2022, 42 (5) 2363-2374; DOI: 10.21873/anticanres.15715
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