Breast Cancer: Targets and Therapy (Dec 2021)

Anticarcinogenic Effects of Odorant Substances Citral, Citrathal R and Cyclovertal on Breast Cancer in vitro

  • Klauser AL,
  • Hirschfeld M,
  • Ritter A,
  • Rücker G,
  • Jäger M,
  • Gundarova J,
  • Weiss D,
  • Juhasz-Böss I,
  • Berner K,
  • Erbes T,
  • Asberger J

Journal volume & issue
Vol. Volume 13
pp. 659 – 673

Abstract

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Anna-Lena Klauser,1 Marc Hirschfeld,1– 3 Andrea Ritter,1,2 Gerta Rücker,1,4 Markus Jäger,1,2 Julia Gundarova,1 Daniela Weiss,1,2 Ingolf Juhasz-Böss,1,2 Kai Berner,1,2 Thalia Erbes,1,2 Jasmin Asberger1,2 1Faculty of Medicine, University of Freiburg, Freiburg, Germany; 2Department of Obstetrics and Gynecology, Medical Center – University of Freiburg, Freiburg, Germany; 3Institute of Veterinary Medicine, University of Göttingen, Göttingen, Germany; 4Institute of Medical Biometry and Statistics, Medical Center – University of Freiburg, Freiburg, GermanyCorrespondence: Jasmin AsbergerDepartment of Obstetrics and Gynecology, Faculty of Medicine and Medical Center – University of Freiburg, Hugstetterstr. 55, Freiburg, 79106, GermanyTel +49 761 270 30020Fax +49 761 270 30370Email [email protected]: In 2020, breast cancer still represents the most common type of cancer in women worldwide. Depending on the specific molecular subtype, clinical breast cancer management comprises surgery, radiotherapy, chemotherapy and targeted therapy. Furthermore, there are some therapeutic approaches from the field of complementary and alternative medicine. Current research focuses on the elucidation of new therapeutic targets for treatment development. Odorant substances affect apoptosis, proliferation and cell cycle in healthy and cancerous cells. Exact signalling pathways involved are not entirely clear. The present study aims to analyse their therapeutic potential in breast cancer.Methods: This study focuses on the effect of commonly used odorant substances (citral, citrathal R, cyclovertal, para-cymol, hexylacetat, herbavert, dihydromyrcerol and limonen) on the breast cancer cell lines MDA-MB-231, T47-D and BT474. Methodologically, this study applied cell culturing, MTT assay for detection of IC50 of the odorant substance, RNA purification followed by qRT-PCR, protein isolation and Western Blot, as well as immunocytochemistry. Further, this study investigates the role of transient receptor potential channel V1 (TRPV1), involved in the mechanisms of action for some odorant substances. Therefore, capsazepine, a TRPV1 antagonist, was used.Results: The odorant substances citral, citrathal R and cyclovertal have significant pro-apoptotic (p < 0.001), anti-proliferative (p < 0.001) and cell cycle-arresting effects measurable in RNA expression as well as in protein levels and immunocytochemical staining. The combination of citral and capsazepine no longer showed significant pro-apoptotic, antiproliferative, and cell cycle inhibitory effects compared to the compounds alone. This indicates that TRPV1 is necessary for the signal transduction of citral.Conclusion: This present study reveals three odorant substances with effects on cell viability, indicating their potential use in breast cancer therapy.Keywords: citral, citrathal R, cyclovertal, odorant substances, olfactory receptor and breast cancer

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