Multi-targeting chemoprevention of Chinese herb formula Yanghe Huayan decoction on experimentally induced mammary tumorigenesis.

Abstract

BACKGROUND:

Development of safe and effective chemopreventive agents is a winning strategy in reducing the morbidity and mortality of breast cancer. The current study was to investigate the mechanism-based chemopreventive potential of a Chinese herb formula Yanghe Huayan (YHHY) Decoction on the classical 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinogenesis model.

METHODS:

Female Sprague-Dawley rats at 42 days of age were orally administered with a human equivalent dose of YHHY Decoction at 0.02 ml/g (10 mg/ml) once daily, starting 1 wk. before and 4 wks following DMBA treatment. Mammary tumor occurrence was monitored every day. The length of time before palpable tumor is examined is defined as tumor-free survival time. High performance liquid chromatography (HPLC) analyses were adopted to identify major chemical compositions of the decoction. Following bioinformatics data mining and experimental analyses were performed to demonstrate the underlying mechanism of action.

RESULTS:

DMBA animals receiving YHHY Decoction exhibited a significant delay (P = 0.014) and in some animals prevention (P = 0.046) of tumor occurrence without obvious toxicity. Oncogenic myc activation was significantly suppressed in the DMBA-induced rats by the YHHY treatment. Eight major chemical compositions of the decoction were identified and were shown to interfere with multiple tumorigenic pathways simultaneously in the mammary tumors, including inducing tumor apoptosis and up-regulating pro-apoptotic protein Bax and down-regulating anti-apoptotic protein Bcl-2; suppressing abnormal cell proliferation and the MAPK/ERK, PI3K/AKT signalings; blocking neo-angiogenesis and the VEGF/KDR signaling, and inhibiting oxidative stress in the mammary tumors.

CONCLUSION:

The multi-components and multi-targeting properties of the YHHY Decoction support its use as a potent chemopreventive drug in breast cancer.

• Authors: Jingwei Li, Xiaofei Liu, Hongzhi Chen, Ziyuan Sun, Hanhan Chen, Lei Wang, Xiaohui Sun, Xiangqi Li
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 19 Issue 1 Pg. 48 (Feb 13 2019) ISSN: 1472-6882 [Electronic] England
• PMID: 30760265 (Publication Type: Journal Article)

Chemical References

• 3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene
• Anthracenes
• Antineoplastic Agents
• Drugs, Chinese Herbal
• Piperidines

Topics

• Administration, Oral
• Animals
• Anthracenes (adverse effects)
• Antineoplastic Agents (pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• Female
• Mammary Neoplasms, Experimental (chemically induced, metabolism, pathology, prevention & control)
• Oxidative Stress (drug effects)
• Piperidines (adverse effects)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)