The anti‐tumor effects of cosmosiin through regulating AhR/CYP1A1PPARγ in breast cancer

Author:

Wang Dan1ORCID,Zhang Jing2ORCID,Yin Houqing1,Yan Ribai3ORCID,Wang Zequn1,Deng Jinhai4ORCID,Li Gang5ORCID,Pan Yan16ORCID

Affiliation:

1. Department of Pharmacology, School of Basic Medical Sciences, Health Science Center Peking University Beijing China

2. Inner Mongolia Key Laboratory of Molecular Biology Inner Mongolia Medical University Hohhot China

3. School of Pharmaceutical Sciences Peking University Beijing China

4. Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences King's College London London UK

5. Department of General Surgery Peking University Third Hospital Beijing China

6. Beijing Key Laboratory of Tumor Systems Biology Peking University Beijing China

Abstract

AbstractBreast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti‐tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti‐breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models in vivo and in vitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells in vitro and suppressed the growth of tumor in vivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/β‐catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti‐breast cancer therapy.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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