Research Article: Naringin targets Zeb1 to suppress osteosarcoma cell proliferation and metastasis

Date Published: December 22, 2018

Publisher: Impact Journals

Author(s): He Ming, Qiu Chuang, Wang Jiashi, Li Bin, Wang Guangbin, Ji Xianglu.


Naringin, a citrus bioflavonoid, has anti-inflammatory actions and cardio- and neuroprotective effects. In addition, naringin exhibits multiple antitumor actions in several cancer types, including osteosarcoma, the most common type of bone cancer. Here, we show that naringin inhibits proliferation and invasion and induces apoptosis in human osteosarcoma cells by inhibiting zinc finger E-box binding homeobox 1 (Zeb1), a transcriptional repressor of epithelial differentiation involved in tumor metastasis. Our expression analyses confirm that Zeb1 is highly expressed in osteosarcoma specimens and cell lines. The effects of naringin, which included downregulation of Cyclin D1, MMP2, and bcl-2, where reproduced by siRNA-mediated Zeb1 silencing, whereas Zeb1 overexpression increased proliferation, migration, and Cyclin D1, MMP2, and bcl-2 levels. In addition, naringin administration reduced tumor nodule formation and attenuated the expression of the above proteins in the livers of mice injected with MG63 osteosarcoma cells. Our study provides preclinical evidence for the potential therapeutic application of naringin in the treatment of osteosarcoma.

Partial Text

Although adjuvant chemotherapy has improved osteosarcoma survival rate in recent years, development of multidrug resistance severely impacts prognosis and restricts success of curative attempts [1–3]. Therefore, new and effective drugs to treat osteosarcoma are clearly needed.

Naringin, a flavonoid present in citrus fruits, has HMG-CoA reductase inhibitor activity, and at low (nM) doses increases osteogenic activities in an osteoblast cell model in vitro [22]. Moreover, naringin-induced osteogenic differentiation has been recently described in bone marrow stromal cells and stem cells [23].On the other hand, naringin has been shown to inhibit cell proliferation and promote cell apoptosis in breast cancer, cervical cancer, melanoma, and bladder cancer cells [24]. Thus, we speculated that naringin may have therapeutic effect on osteosarcoma as well.




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