Oncotarget

Research Papers:

Eugenol alleviated breast precancerous lesions through HER2/ PI3K-AKT pathway-induced cell apoptosis and S-phase arrest

Min Ma _, Yi Ma, Gui-Juan Zhang, Rui Liao, Xue-Feng Jiang, Xian-Xin Yan, Feng-Jie Bie, Xiao-Bo Li and Yan-Hong Lv

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Oncotarget. 2017; 8:56296-56310. https://doi.org/10.18632/oncotarget.17626

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Abstract

Min Ma1,*, Yi Ma2,*, Gui-Juan Zhang3,*, Rui Liao1, Xue-Feng Jiang1, Xian-Xin Yan1, Feng-Jie Bie1, Xiao-Bo Li1 and Yan-Hong Lv1

1College of Traditional Chinese Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China

2Institute of Biomedicine, Department of Cellular Biology, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou 510632, Guangdong Province, China

3The First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China

*These authors contributed equally to this work

Correspondence to:

Min Ma, email: [email protected], [email protected]

Keywords: eugenol, breast precancerous lesion, HER2/PI3K-AKT, external use, cell apoptosis

Received: February 18, 2017     Accepted: April 19, 2017     Published: May 05, 2017

ABSTRACT

Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3.1-HER2. In MCF-10AT cells treated by 180 μM eugenol, the protein expressions of HER2, AKT, PDK1, p85, Bcl2, NF-κB, Bad and Cyclin D1 were decreased and the decreased rates were respectively 63.0%, 60.0%, 52.9%, 62.9%, 37.1%, 47.2%, 61.7%, 59.1%, while the p21, p27 and Bax expression were increased by 4.48-, 4.76- and 2.57-fold respectively. In the rat models of breast precancerous lesion, 1 mg eugenol for external use significantly inhibited the progress of breast precancerous lesion and the occurrence rate of breast precancerous lesions and invasive carcinomas was decreased by about 30.5%. Furthermore eugenol for external (1 mg) markedly decreased the protein expressions of HER2 (62.9%), AKT (58.6%), PDK1 (56.4%), p85 (54.3%), Bcl2 (59.3%), NF-κB (65.7%), Bad (64.0%), Cyclin D1 (43.0%), while p21, p27 and Bax protein expressions were respectively increased 1.83-, 2.52- and 2.51-fold. The results showed eugenol could significantly inhibit the development of breast precancerous lesions by blocking HER2/PI3K-AKT signaling network. So eugenol may be a promising external drug for breast precancerous lesions.


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