Abstract
Apigenin is a natural flavone with anti-inflammatory and antioxidant properties and antitumor abilities against several types of cancers. Previous studies have found that the antitumor effects of apigenin may be due to its similar chemical structure to 17β-estradiol (E2), a main kind of estrogen in women. However, the precise mechanism underlying the antitumor effects of apigenin in cervical cancer remains unknown. On the other hand, there is increasing evidence that describes a histamine role in cancer cell proliferation. In this study, we examined whether apigenin can attenuate the effects of histamine on tumors by regulating the expression level of estrogen receptors (ERs) to inhibit cervical cancer growth. Our in vitro data indicates that apigenin inhibited cell proliferation in a dose-dependent manner in human cervical cancer cells (HeLa), while histamine shows the opposite effects. After that, the xenograft model was established to explore the antitumor effects of apigenin in vivo, the results show that apigenin inhibited cervical tumor growth by reversing the abnormal ER signal in tumor tissue which was caused by histamine. We also demonstrate that apigenin inhibited cell proliferation via suppressing the PI3K/Akt/mTOR signaling pathway. Collectively, our results suggest that apigenin may inhibit tumor growth through the ER-mediated PI3K/Akt/mTOR pathway and that it can also attenuate the effects of histamine on tumors.
Highlights
Cervical cancer, as a gynecological tumor, remains one of the most common causes of cancer-related deaths worldwide, which consists of 528,000 new cases and 266,000 deaths worldwide each year [1,2].Most of the cervical cancer cases result from infection with human papillomavirus, and the primary treatment options for these patients include surgery followed by radiotherapy [3]
After incubation with histamine for 48 h, we found that the proliferation of human cervical cancer cells (HeLa) cells was stimulated by histamine in a dose-dependent manner between the concentration of 1 ng/mL and 10 ng/mL (Figure 1A)
The cell proliferation was slightly lower in 100 ng/mL compared to 50 ng/mL, this probably can be explained by the cytotoxicity of histamine at a high concentration
Summary
As a gynecological tumor, remains one of the most common causes of cancer-related deaths worldwide, which consists of 528,000 new cases and 266,000 deaths worldwide each year [1,2]. Most of the cervical cancer cases result from infection with human papillomavirus, and the primary treatment options for these patients include surgery followed by radiotherapy [3]. In those underdeveloped countries which grossly lack sufficient treatment, cervical cancer causes more than one quarter of a million deaths per year [5]. Various bioactive natural compounds have already been well studied and shown to be useful in prevention and therapy of cancer by regulating numerous signaling pathways. According to a previous published review, drugs targeting cancer approved by the United
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