Amentoflavone suppresses tumor growth in ovarian cancer by modulating Skp2.

Abstract

AIM:

Ovarian cancer is one of most common malignancies in women and is associated with high reoccurrence rate and poor prognosis. This study is designed to investigate the anti-tumor effects of amentoflavone (AF), one of the major active ingredients of S. tamariscina, against ovarian cancer.

MATERIALS AND METHODS:

Human ovarian cancer cell lines SKOV3 and OVCAR-3 were used in this study. The effect of AF on cell viability was examined by CCK-8 assay. Cell apoptosis and cell cycle distribution was determined by flow cytometry. ROS generation was detected using fluorescent staining. Expression of signaling molecules was determined by western blots. Xenograft model was established to evaluate the therapeutic efficacy of AF in vivo.

KEY FINDINGS:

Our results showed that AF could significantly suppress cell proliferation, induce apoptosis and block cell cycle progression. Mechanistically, downregulation of S-phase kinase protein 2 (Skp2) by AF contributed to its anti-tumor effect against ovarian cancer. Furthermore, our results showed that AF repressed the expression of Skp2 through ROS/AMPK/mTOR signaling. The anti-tumor effect of AF against ovarian cancer was also confirmed in a xenograft animal model.

SIGNIFICANCE:

Overall, our present findings highlighted the potential of AF in the treatment of ovarian cancer. Moreover, our study also provided a new elucidation regarding the anti-tumor mechanisms of AF.

• Authors: Honggai Liu, Qingfen Yue, Shehong He
• Journal: Life sciences (Life Sci) Vol. 189 Pg. 96-105 (Nov 15 2017) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 28942285 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Biflavonoids
• S-Phase Kinase-Associated Proteins
• amentoflavone

Topics

• Animals
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Biflavonoids (isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• S-Phase Kinase-Associated Proteins (genetics)
• Selaginellaceae (chemistry)
• Xenograft Model Antitumor Assays