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

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

Manal Mohammad Abbas  1 , Yasser İbrahim Kandil  2   3 , Manal Ahmad Abbas  1
Affiliations

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

Manal Mohammad Abbas et al. Balkan Med J. .

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.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
Scheme for experimental design. DOX: Doxorubicin
Figure 2
Figure 2
Histology of heart tissue from mice receiving only vehicle (A), DOX (B), R-(-)-carvone (75 mg/kg) plus DOX (C), and R-(-)-carvone (150 mg/kg) plus DOX (D). Note myocardial fiber injury in B represented by vacuolation of the cytoplasm (circles). Also, congestion in blood vessels is obvious (black arrow). R-(-)-carvone 150 mg/kg in D protected the heart from the effects of DOX (H&E stain). DOX: doxorubicin
Figure 3
Figure 3
Cytotoxic effect of R-(-)-carvone alone or in combination with Dox in H9C2, and MCF 7 cell lines. Carvone decreased the cytotoxicity of DOX in H9C2 cells (A) and enhanced the cytotoxicity of DOX in MCF 7 cells (B). The IC50 value of all treatments was measured by the MTT assay. DOX: doxorubicin
Figure 4
Figure 4
Results of catalase activity in normal heart in vivo. Catalase activity was increased by R-(-)-carvone alone or by R-(-)-carvone/DOX combination in normal heart in vivo (A). Catalase activity in in the heart cell line (H9C2). Both doses of R-(-)-carvone alone and the combination of R-(-)-carvone with DOX increased catalase activity in the heart cell line (B). DOX: doxorubicin
See this image and copyright information in PMC

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