OBJECTIVEThis study aims to investigate the impact of Polyphyllin VII (PP7) on pulmonary hypertension (PH) and elucidate the underlying mechanism involving microRNA (miR)-205-5p/β-catenin.METHODSThe PH rat model was induced through hypoxia exposure. The effects of intraperitoneal injection of PP7 on pulmonary artery tissue pathology, hemodynamics, miR-205-5p expression and β-catenin protein levels were assessed. In vitro, pulmonary arterial smooth muscle cells (PASMCs) were subjected to hypoxic conditions. Moreover, miR-205-5p and/or β-catenin were overexpressed through transfection. PASMCs were pre-cultured in 20 μM PP7, and subsequent measurements included proliferation, apoptosis and vascular remodeling protein expression.RESULTSPP7 ameliorated PH symptoms in rats, upregulated miR-205-5p expression and inhibited β-catenin protein expression. Furthermore, miR-205-5p upregulation inhibited β-catenin expression in PASMCs. The overexpression of β-catenin aggravated hypoxia-induced proliferation, inhibited apoptosis and further augmented VEGF and α-SMA protein expression. Additionally, miR-205-5p overexpression alleviated the hypoxia-induced PASMC proliferation and apoptosis by inhibiting β-catenin protein expression. Under hypoxic conditions, PP7 significantly elevated miR-205-5p while downregulating β-catenin protein expression. Furthermore, inhibiting miR-205-5p counteracted the inhibitory effect of PP7 on β-catenin, consequently blocking the regulatory role of PP7 in PASMC proliferation and apoptosis.CONCLUSIONPP7 likely modulates β-catenin protein levels by promoting miR-205-5p expression, thereby alleviating PH, vascular remodeling and airway smooth muscle remodeling.

01 Jul 2023·International Immunopharmacology

Polyphyllin VII protects from breast cancer-induced osteolysis by suppressing osteoclastogenesis via c-Fos/NFATc1 signaling

Article

Author: Li, Lihong ; Zou, Binhua ; Mo, Lixia ; Yang, Qin ; Chen, Yan ; Chen, Ziye ; Ding, Zongbao ; Li, Xiaojuan ; Zheng, Jiehuang ; Li, Ruopeng ; Chen, Fengsheng ; Guo, Jingyun ; Wang, Yiyuan ; Liang, Qinghe

Bone is a preferred metastatic site of advanced breast cancer and the 5-year overall survival rate of breast cancer patients with bone metastasis is only 22.8%. Targeted inhibition of osteoclasts can treat skeletal-related events (SREs) in breast cancer patients. Polyphyllin VII (PP7), a pennogenyl saponin isolated from traditional Chinese herb Paris polyphylla, exhibits strong anti-inflammatory and anti-cancer activities. In this study, we evaluated the effect of PP7 on metastatic breast cancer-induced bone destruction in vivo and the underlying mechanisms. We found that intraperitoneal injection of 1 mg/kg PP7 significantly ameliorated the breast cancer MDA-MB-231 cell-induced osteolysis in mice. Mechanistically, PP7 (0.125-0.5 μM) inhibited the conditioned medium of MDA-MB-231 cells (MDA-MB-231 CM)-induced osteoclast formation in bone marrow-derived macrophages (BMMs). Furthermore, PP7 markedly reduced MDA-MB-231 CM-induced osteoclastic bone resorption and F-actin rings formation in vitro. During MDA-MB-231 CM-induced osteoclastogenesis, the activation of c-Fos and NFATc1 signaling was significantly downregulated by PP7, and finally osteoclast-related genes such as Oscar, Atp6v0d2, Mmp9 and β3 integrin were decreased. In addition, the formation of osteoblast was promoted by PP7 treatment. Our current findings revealed PP7 as a potential safe agent for preventing and treating bone destruction in breast cancer patients with bone metastases.

01 Apr 2023·Current Cancer Drug Targets

Polyphyllin VII as a Potential Drug for Targeting Stemness in Hepatocellular Cancer via STAT3 Signaling

Article

Author: Xi, Xueyan ; Li, Fangzhou ; Wang, Zhongyu ; Xu, Liuhang ; Li, Yulin ; Chen, Ziqi ; Wang, Yangbin

Background:At present, the treatment of hepatocellular carcinoma (HCC) is disturbed by the treatment failure and recurrence caused by the residual liver cancer stem cells (CSCs). Therefore, drugs targeting HCC CSCs should be able to effectively eliminate HCC and prevent its recurrence. In this study, we demonstrated the effect of Polyphyllin VII (PP7) to HCC CSCs, and explored their potential mechanism.Methods:HepG2 and Huh7 cells, were used to analyze the antitumor activity of PP7 by quantifying cell growth and metastasis as well as to study the effect on stemness.Results:Our results demonstrated that PP7 promoted apoptosis and significantly inhibited proliferation and migration of both HepG2 and Huh7 cells. PP7 also inhibited tumor spheroid formation and induced significant changes in the expression of stemness markers (CD133 and OCT-4). These effects of PP7 were mediated by the STAT3 signaling.Conclusion:PP7 can effectively suppress tumor initiation, growth, metastasis, and inhibit stemness through regulation of STAT3 signaling pathway in liver cancer cells. Our data would add more evidence to further clarify the therapeutic effect of PP7 against HCC.

100 Deals associated with PP7(University of Florida)

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	United States	University of Florida	17 Sep 2021

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