Amentoflavone suppresses tumor growth in ovarian cancer by modulating Skp2
Authors: Honggai Liu
Qingfen Yue
Shehong He
Journal: Life Sciences (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AMPK; Amentoflavone; Ovarian cancer; Skp2.
Affiliations: Department of Gynaecology, Luoyang Central Hospital, Zhengzhou University, China., Department of Gynaecology, Luoyang Central Hospital, Zhengzhou University, China. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 At left, Fig 7C,  AF suppresses ovarian tumor growth in vivo. .... C. Tumor weight measurement showed exertion of anti-tumor effects in vivo by AF. At right, Fig 4A from [Pan et al (2019)] ,  Combination therapy of physcion and sorafenib significantly suppresses the tumor growth in vivo. (A) Combination of physcion and sorafenib can markedly suppress tumor growth . ![file] Same tumors appearing in two papers by unconnected teams of authors, illustrating how different combinations of chemicals suppressed their growth. , 
 Left: Fig 7D,  AF suppresses ovarian tumor growth in vivo. .... D. TUNEL, HE and immunohiostochemical assay showed AF induced apoptosis and downregulated Skp2 in vivo. At right: Fig 4B from [Wang et al (2018)] ,  MiR-137 exerts anti-tumor effect in vivo. A). ... B). Inhibition of miR-137 on [renal] tumor growth correlates with lower expression of RLIP76 and higher expression of cleaved caspase-3. ![file] Could the authors clarify whether these images came from ovarian or renal tumors? And which markers they show? And which treatments applied? And who wrote these papers? , 
 Now comparing (left) Fig 7D with (at right) Fig 7E from [Chen et al (2020)] .  AF inhibits [glioma] tumor growth by triggering autophagy-dependent ferroptosis in vivo. ... (E) The levels of LC3B, Becin1, ATG5, ATG7, and FTH were detected by immunohistochemistry . ![] Uncertainty as to the type of tumor, treatments and the IHC targets is heightened by the lack of authors in common between the two papers. , 
 #1 ![] UPDATE: Rotated versions: Fig 5B of [Du et al (2019)] .  Anti-tumor activities of PG in vivo. ... (B) PG dose-dependently decreased the [lung] tumor weight. ![file] , 
 #4 Fig 7B:  AF suppresses ovarian tumor growth in vivo. ... B. Tumor volume measurement showed that AF suppressed tumor growth in a dose-dependent manner. Below: Fig 7A,  In vivo anti-[osteosarcoma] tumor effect of PG , from [Wang Yang (2016)] . ![file] Different cancer, treatment, and authors. Same mice. ,