Combined treatment with modulated electro-hyperthermia and an autophagy inhibitor effectively inhibit ovarian and cervical cancer growth

Wookyeom Yang, Gwan Hee Han, Ha Yeon Shin, Eun Ju Lee, Hanbyoul Cho, Doo Byung Chay, Jae-Hoon Kim

Research output: Contribution to journalArticle

Abstract

Purpose: Modulated electro-hyperthermia (mEHT), known as oncothermia, is an anticancer therapy that induces radiofrequency thermal damage to the cancer tissues. This study aimed to evaluate the potential effectiveness of mEHT as a therapeutic tool in ovarian and cervical cancer. Materials and methods: We used both tumor-bearing mice and ovarian and cervical OVCAR-3, SK-OV-3, HeLa and SNU-17 cancer cell lines to investigate the effects of mEHT in vivo and in vitro, respectively, and determine whether it was enhanced by cotreatment with an autophagy inhibitor. Results: We discovered that phosphorylation of p38, a stress-dependent kinase, was induced at the Thr180/Tyr182 residue in cancer cells exposed to mEHT. Apoptotic markers such as cleaved caspase-3 and poly-ADP ribose polymerase (PARP) were increased in OVCAR-3 and SNU-17 cells. Fluorescence-activated cell sorting (FACS) analysis showed a significant increase in the population of sub-G1 mEHT-exposed cells, which are dying and apoptotic cells. mEHT also reduced both weight and volume of xenograft tumors in mice transplanted with ovarian and cervical cancer cells and patient-derived cancer tissues. We determined that mEHT-induced cellular damage recovery was mediated by autophagy and, therefore, expectedly, cotreatment with mEHT and 3-methyladenine (3-MA), an autophagy inhibitor, more effectively inhibited cancer cell growth than individual treatment did. Conclusions: mEHT treatment alone was sufficient to inhibit cancer growth, while a combined treatment with mEHT and an autophagy inhibitor amplified this inhibition effect.

Original languageEnglish
Pages (from-to)9-20
Number of pages12
JournalInternational Journal of Hyperthermia
Volume36
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

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Autophagy
Uterine Cervical Neoplasms
Ovarian Neoplasms
Fever
Growth
Neoplasms
Therapeutics
Induced Hyperthermia
Poly(ADP-ribose) Polymerases
Tumor Burden
Heterografts
Caspase 3
Flow Cytometry
Phosphotransferases
Hot Temperature
Phosphorylation
Weights and Measures
Cell Line

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)
  • Cancer Research

Cite this

Yang, Wookyeom ; Han, Gwan Hee ; Shin, Ha Yeon ; Lee, Eun Ju ; Cho, Hanbyoul ; Chay, Doo Byung ; Kim, Jae-Hoon. / Combined treatment with modulated electro-hyperthermia and an autophagy inhibitor effectively inhibit ovarian and cervical cancer growth. In: International Journal of Hyperthermia. 2019 ; Vol. 36, No. 1. pp. 9-20.
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Combined treatment with modulated electro-hyperthermia and an autophagy inhibitor effectively inhibit ovarian and cervical cancer growth. / Yang, Wookyeom; Han, Gwan Hee; Shin, Ha Yeon; Lee, Eun Ju; Cho, Hanbyoul; Chay, Doo Byung; Kim, Jae-Hoon.

In: International Journal of Hyperthermia, Vol. 36, No. 1, 01.01.2019, p. 9-20.

Research output: Contribution to journalArticle

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AU - Yang, Wookyeom

AU - Han, Gwan Hee

AU - Shin, Ha Yeon

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AU - Chay, Doo Byung

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N2 - Purpose: Modulated electro-hyperthermia (mEHT), known as oncothermia, is an anticancer therapy that induces radiofrequency thermal damage to the cancer tissues. This study aimed to evaluate the potential effectiveness of mEHT as a therapeutic tool in ovarian and cervical cancer. Materials and methods: We used both tumor-bearing mice and ovarian and cervical OVCAR-3, SK-OV-3, HeLa and SNU-17 cancer cell lines to investigate the effects of mEHT in vivo and in vitro, respectively, and determine whether it was enhanced by cotreatment with an autophagy inhibitor. Results: We discovered that phosphorylation of p38, a stress-dependent kinase, was induced at the Thr180/Tyr182 residue in cancer cells exposed to mEHT. Apoptotic markers such as cleaved caspase-3 and poly-ADP ribose polymerase (PARP) were increased in OVCAR-3 and SNU-17 cells. Fluorescence-activated cell sorting (FACS) analysis showed a significant increase in the population of sub-G1 mEHT-exposed cells, which are dying and apoptotic cells. mEHT also reduced both weight and volume of xenograft tumors in mice transplanted with ovarian and cervical cancer cells and patient-derived cancer tissues. We determined that mEHT-induced cellular damage recovery was mediated by autophagy and, therefore, expectedly, cotreatment with mEHT and 3-methyladenine (3-MA), an autophagy inhibitor, more effectively inhibited cancer cell growth than individual treatment did. Conclusions: mEHT treatment alone was sufficient to inhibit cancer growth, while a combined treatment with mEHT and an autophagy inhibitor amplified this inhibition effect.

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