R-(-)-carvone Attenuated Doxorubicin Induced Cardiotoxicity In Vivo and Potentiated Its Anticancer Toxicity In Vitro

Balkan Med J. 2020 Feb 28;37(2):98-103. doi: 10.4274/balkanmedj.galenos.2019.2019.7.117. Epub 2020 Jan 2.

Abstract

Background: Doxorubicin is one of the most potent broad-spectrum antitumor and chemotherapeutic agents. However, it produces cardiotoxicity.

Aims: To investigate whether R-(-)-carvone exerts a cardioprotective effect against doxorubicin toxicity in vivo and in vitro.

Study design: Cell culture and animal experiment.

Methods: The synergistic effect of R-(-)-carvone with doxorubicin was evaluated in the MCF 7 cancer cell line while its protective effect against doxorubicin toxicity was evaluated in the normal heart cell line (H9C2) and in vivo. Furthermore, the mechanism of its cardioprotective effect was studied.

Results: R-(-)-carvone exerted cytotoxic action on the MCF 7 cancer cell line with an IC50 value of 14.22 μM and potentiated the cytotoxic action of doxorubicin, while it decreased the toxicity of doxorubicin on a normal heart cell line. In BALB/c mice, R-(-)-carvone protected the heart from the toxic action of doxorubicin, as was evident by biochemical and histological studies. The protective effect of R-(-)-carvone on the H9C2 heart cell line and on heart in vivo was due to an increase in catalase activity.

Conclusion: R-(-)-carvone has synergistic anticancer action with doxorubicin on the MCF 7 cell line while decreasing its cardiotoxicity.

Keywords: Cardiotoxicity; R-(-)-carvone; H9C2; catalase; doxorubicin; MCF 7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / standards
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Cardiotoxicity / drug therapy
  • Cardiotoxicity / prevention & control*
  • Cyclohexane Monoterpenes / pharmacology
  • Cyclohexane Monoterpenes / standards
  • Cyclohexane Monoterpenes / therapeutic use*
  • Disease Models, Animal
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity*
  • Heart / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Protective Factors

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Cyclohexane Monoterpenes
  • carvone
  • Doxorubicin