Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells

Mustafa Nazıroğlu, Walter Blum, Katalin Jósvay, Bilal Çiğ, Thomas Henzi, Zoltán Oláh, Csaba Vizler, Beat Schwaller, László Pecze

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca2+ signals in breast and prostate cancer cell lines. The effect of menthol (50–500 µM) was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8). However, the intensity of menthol-evoked Ca2+ signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway. Menthol-evoked Ca2+ signals were analyzed in detail in Du 145 prostate cancer cells, as well as in CRISPR/Cas9 TRPM8-knockout Du 145 cells. Menthol (500 µM) induced Ca2+ oscillations in both cell lines, thus independent of TRPM8, which were however dependent on the production of inositol trisphosphate. Results based on pharmacological tools point to an involvement of the purinergic pathway in menthol-evoked Ca2+ responses. Finally, menthol (50–500 µM) decreased cell viability and induced oxidative stress independently of the presence of TRPM8 channels, despite that temperature-evoked TRPM8-mediated inward currents were significantly decreased in TRPM8-knockout Du 145 cells compared to wild type Du 145 cells.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalRedox Biology
Volume14
DOIs
Publication statusPublished - Apr 1 2018

Fingerprint

Menthol
Transient Receptor Potential Channels
Oxidative stress
Ion Channels
Oxidative Stress
Cells
Neoplasms
Prostatic Neoplasms
Antipruritics
Clustered Regularly Interspaced Short Palindromic Repeats
Breast Neoplasms
Cell Line
Monoterpenes
Local Anti-Infective Agents
Non-Steroidal Anti-Inflammatory Agents
Inositol
Analgesics
Cell Survival
Anti-Inflammatory Agents
Alcohols

Keywords

  • Ca oscillations
  • Menthol
  • Oxidative stress
  • Purinergic signaling
  • TRPM8

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells. / Nazıroğlu, Mustafa; Blum, Walter; Jósvay, Katalin; Çiğ, Bilal; Henzi, Thomas; Oláh, Zoltán; Vizler, Csaba; Schwaller, Beat; Pecze, László.

In: Redox Biology, Vol. 14, 01.04.2018, p. 439-449.

Research output: Contribution to journalArticle

Nazıroğlu, Mustafa ; Blum, Walter ; Jósvay, Katalin ; Çiğ, Bilal ; Henzi, Thomas ; Oláh, Zoltán ; Vizler, Csaba ; Schwaller, Beat ; Pecze, László. / Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells. In: Redox Biology. 2018 ; Vol. 14. pp. 439-449.
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