Induction of apoptotic cell death by Pharbitis nil extract in HER2-overexpressing MCF-7 cells

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• 作者：Ji-hyun Ju^a ; Min Jeong Jeon^a ; Wonseok Yang^a ; Kyung-min Lee^a ; Hye-Sook Seo^a ; Incheol Shin ; ^a ; ^{incheol@hanyang.ac.kr}
• 关键词：Akt ; Apoptosis ; Breast cancer ; ERK ; HER2 ; Pharbitis nil
• 刊名：Journal of Ethnopharmacology
• 出版年：2011
• 出版时间：7 January 2011
• 年：2011
• 卷：133
• 期：1
• 页码：126-131
• 全文大小：815 K

文摘

Aim of the study

We performed this study to investigate the anti-cancer activity of Pharbitis nil (PN) ethanol extract which has been used for herbal medicinal treatment against diseases in East Asia.

Materials and methods

We analyzed the effects of PN extract on proliferation of breast cancer cell lines, MCF-7 control vector (vec) and MCF-7 human epidermal growth factor receptor 2 (HER2) cells engineered to overexpress oncogenic HER2 via retroviral infection. We performed the proliferation assay to measure the growth rate of the cells. FACS analysis was used to analyze the cell cycle. Western blot analysis was used to investigate the effect of PN on the level and activation of intracellular molecules.

Results

We found that PN extract inhibited the proliferation of both MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with the increase of sub G0/G1 apoptotic fractions. When we check the efficiency of PN on the level of intracellular signaling molecules, we found that PN extract induced the inhibition of phosphorylation of HER2 and its downstream effectors, Akt and extracellular signal-regulated kinases (ERK). Active forms of both Akt and ERK were gradually decreased in PN-treated MCF-7 vec and MCF-7 HER2 cells suggesting that the growth suppressive activity of PN is related to signaling pathway. The level of cyclin D also diminished in PN-treated both cells suggesting that PN may inhibit the growth of MCF-7 vec and MCF-7 HER2 cells by perturbing cell cycle progression. It should be noted that PN decreased the growth rate of both MCF-7 vec and MCF-7 HER2 cells without changing the level and activation of p53.

Conclusion

PN extract suppressed the proliferation rate of HER-2 overexpressing MCF-7 breast cancer cells inducing apoptotic cell death in vitro. Our data demonstrates that PN extracts contain useful anti-tumor activity especially against HER2 overexpressing breast cancer.