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Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats and Potentiates Its Anticancer Activity on MCF-7 Cells

View Article: PubMed Central - PubMed

ABSTRACT

Cardiotoxicity is a limiting factor of doxorubicin (DOX)-based anticancer therapy. Due to its beneficial effects, we investigated whether standardized extract of Melissa officinalis (MO) can attenuate doxorubicin-induced cardiotoxicity and can potentiate the efficacy of DOX against human breast cancer cells. MO was administered orally to male albino rats once daily for 10 consecutive days at doses of 250, 500 and 750 mg/kg b.wt. DOX (15 mg/kg b.wt. i.p.) was administered on the 8th day. MO protected against DOX-induced leakage of cardiac enzymes and histopathological changes. MO ameliorated DOX-induced oxidative stress as evidenced by decreasing lipid peroxidation, protein oxidation and total oxidant capacity depletion and by increasing antioxidant capacity. Additionally, MO pretreatment inhibited inflammatory responses to DOX by decreasing the expressions of nuclear factor kappa-B, tumor necrosis factor-alpha and cyclooxygenase-2 and the activity of myeloperoxidase. MO ameliorated DOX-induced apoptotic tissue damage in heart of rats. In vitro study showed that MO augmented the anticancer efficacy of DOX in human breast cancer cells (MCF-7) and potentiated oxidative damage and apoptosis. Thus, combination of DOX and MO may prove future cancer treatment protocols safer and more efficient.

No MeSH data available.


Effect of MO on cardiac apoptotic effect of DOX-treated rats.(A) Gel photograph depicting western blot analysis of bax and caspase-3 protein expression in heart of experimental animals. (B) Graphs present the relative expression of bax and caspase-3. Data are expressed as fold change (relative to control group) and as mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX.
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pone.0167049.g004: Effect of MO on cardiac apoptotic effect of DOX-treated rats.(A) Gel photograph depicting western blot analysis of bax and caspase-3 protein expression in heart of experimental animals. (B) Graphs present the relative expression of bax and caspase-3. Data are expressed as fold change (relative to control group) and as mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX.

Mentions: Protein expression of programed cell death (apoptosis) markers such as Bax and caspase- 3 were assessed in all tested groups using Western Blotting. Protein levels of Bax and caspase- 3 were significantly increased in DOX-treated rats compared to control. The DOX-induced upregulated expression of Bax and caspase- 3 proteins was significantly reduced in a dose-dependent manner by pretreatment with MO. Levels of protein expression of Bax and caspase-3 were not altered in animal group treated with MO alone, compared to the control group (Fig 4).


Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats and Potentiates Its Anticancer Activity on MCF-7 Cells
Effect of MO on cardiac apoptotic effect of DOX-treated rats.(A) Gel photograph depicting western blot analysis of bax and caspase-3 protein expression in heart of experimental animals. (B) Graphs present the relative expression of bax and caspase-3. Data are expressed as fold change (relative to control group) and as mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX.
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Related In: Results  -  Collection

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pone.0167049.g004: Effect of MO on cardiac apoptotic effect of DOX-treated rats.(A) Gel photograph depicting western blot analysis of bax and caspase-3 protein expression in heart of experimental animals. (B) Graphs present the relative expression of bax and caspase-3. Data are expressed as fold change (relative to control group) and as mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX.
Mentions: Protein expression of programed cell death (apoptosis) markers such as Bax and caspase- 3 were assessed in all tested groups using Western Blotting. Protein levels of Bax and caspase- 3 were significantly increased in DOX-treated rats compared to control. The DOX-induced upregulated expression of Bax and caspase- 3 proteins was significantly reduced in a dose-dependent manner by pretreatment with MO. Levels of protein expression of Bax and caspase-3 were not altered in animal group treated with MO alone, compared to the control group (Fig 4).

View Article: PubMed Central - PubMed

ABSTRACT

Cardiotoxicity is a limiting factor of doxorubicin (DOX)-based anticancer therapy. Due to its beneficial effects, we investigated whether standardized extract of Melissa officinalis (MO) can attenuate doxorubicin-induced cardiotoxicity and can potentiate the efficacy of DOX against human breast cancer cells. MO was administered orally to male albino rats once daily for 10 consecutive days at doses of 250, 500 and 750 mg/kg b.wt. DOX (15 mg/kg b.wt. i.p.) was administered on the 8th day. MO protected against DOX-induced leakage of cardiac enzymes and histopathological changes. MO ameliorated DOX-induced oxidative stress as evidenced by decreasing lipid peroxidation, protein oxidation and total oxidant capacity depletion and by increasing antioxidant capacity. Additionally, MO pretreatment inhibited inflammatory responses to DOX by decreasing the expressions of nuclear factor kappa-B, tumor necrosis factor-alpha and cyclooxygenase-2 and the activity of myeloperoxidase. MO ameliorated DOX-induced apoptotic tissue damage in heart of rats. In vitro study showed that MO augmented the anticancer efficacy of DOX in human breast cancer cells (MCF-7) and potentiated oxidative damage and apoptosis. Thus, combination of DOX and MO may prove future cancer treatment protocols safer and more efficient.

No MeSH data available.