What is the clinical evidence from this study?

Study design: Other. Population: Liver Cancer. Intervention: Quercetin and Doxorubicin vs. Doxorubicin alone. Primary outcome: Average tumor weight (p=<0.001).

December 11, 2012PLoS ONE153 citationsOpen Access

Quercetin Potentiates Doxorubicin Mediated Antitumor Effects against Liver Cancer through p53/Bcl-xl

Q: What are the key findings of this study?

The combined treatment of quercetin and doxorubicin significantly reduced the average tumor weight of liver cancer xenografts to 20 mg compared to 87 mg with doxorubicin alone.

GWGuanyu Wang JZJiawei Zhang LLLuying Liu

Key Result

The combined treatment of quercetin and doxorubicin significantly reduced the average tumor weight of liver cancer xenografts to 20 mg compared to 87 mg with doxorubicin alone.

Structured PICO

Does quercetin improve doxorubicin-mediated antitumor effects and prevent hepatotoxicity in liver cancer models?

Population

Liver cancer cells (SMMC7721, QGY7701), normal liver cells (L02), immune-deficient nude mice with SMMC7721 xenografts (n=20), and C57BL/6 mice (n=24)

Intervention

Quercetin (in vitro: 20 mM; in vivo: 100 mg/kg i.p.) combined with doxorubicin (in vitro: 1 mM; in vivo: 4 mg/kg or 20 mg/kg i.p.)

Comparator

Doxorubicin alone, quercetin alone, and normal saline vehicle control

Outcome

Tumor growth inhibition (tumor volume and weight) and hepatotoxicity (serum ALT/AST levels and histological changes)surrogate

Quercetin potentiates the antitumor efficacy of doxorubicin against liver cancer while protecting against doxorubicin-induced hepatotoxicity in preclinical models.

Main Result

Absolute Event Rate: 20% vs 87%

p-value: p=<0.001

Abstract

BACKGROUND: The dose-dependent toxicities of doxorubicin (DOX) limit its clinical applications, particularly in drug-resistant cancers, such as liver cancer. In this study, we investigated the role of quercetin on the antitumor effects of DOX on liver cancer cells and its ability to provide protection against DOX-mediated liver damage in mice. METHODOLOGY AND RESULTS: The MTT and Annexin V/PI staining assay demonstrated that quercetin selectively sensitized DOX-induced cytotoxicity against liver cancer cells while protecting normal liver cells. The increase in DOX-mediated apoptosis in hepatoma cells by quercetin was p53-dependent and occurred by downregulating Bcl-xl expression. Z-VAD-fmk (caspase inhibitor), pifithrin-α (p53 inhibitor), or overexpressed Bcl-xl decreased the effects of quercetin on DOX-mediated apoptosis. The combined treatment of quercetin and DOX significantly reduced the growth of liver cancer xenografts in mice. Moreover, quercetin decreased the serum levels of alanine aminotransferase and aspartate aminotransferase that were increased in DOX-treated mice. Quercetin also reversed the DOX-induced pathological changes in mice livers. CONCLUSION AND SIGNIFICANCE: These results indicate that quercetin potentiated the antitumor effects of DOX on liver cancer cells while protecting normal liver cells. Therefore, the development of quercetin may be beneficial in a combined treatment with DOX for increased therapeutic efficacy against liver cancer.

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