Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein.
Xiaoguang Li,Qian Ba,Yanling Liu,Qingxi Yue,Peizhan Chen,Jingquan Li,Haibing Zhang,Hao Ying,Qiurong Ding,Haiyun Song,Hong Liu,Ruiwen Zhang,Hui Wang,Hui Wang +13 more
TLDR
Dihydroartemisinin, one of the most active derivatives of ArtemisinIn, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to inhibit ovarian cancer cell growth and metastasis and shed high light on future development of novel Artemisinin-based targeted therapy.Abstract:
To develop traditional medicines as modern pharmacotherapies, understanding their molecular mechanisms of action can be very helpful. We have recently reported that Artemisinin and its derivatives, which are clinically used anti-malarial drugs, have significant effects against ovarian cancer, but the direct molecular targets and related combination therapy have been unclear. Herein, we report that dihydroartemisinin, one of the most active derivatives of Artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to inhibit ovarian cancer cell growth and metastasis. Dihydroartemisinin directly binds to the intercellular domain of PDGFRα, reducing its protein stability by accelerating its ubiquitin-mediated degradation, which further inactivates downstream phosphoinositide 3-Kinase and mitogen-activated protein kinase pathways and subsequently represses epithelial–mesenchymal transition, inhibiting cell growth and metastasis of PDGFRα-positive ovarian cancer in vitro and in vivo. A combinational treatment reveals that dihydroartemisinin sensitizes ovarian cancer cells to PDGFR inhibitors. Our clinical study also finds that PDGFRα is overexpressed and positively correlated with high grade and metastasis in human ovarian cancer. Considering that Artemisinin compounds are currently clinically used drugs with favorable safety profiles, the results from this study will potentiate their use in combination with clinically used PDGFRα inhibitors, leading to maximal therapeutic efficacy with minimal adverse effects in PDGFRα-positive cancer patients. These findings also shed high light on future development of novel Artemisinin-based targeted therapy.read more
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Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.
Hua Luo,Chi Teng Vong,Hanbin Chen,Yan Gao,Peng Lyu,Ling Qiu,Mingming Zhao,Qiao Liu,Zehua Cheng,Jian Zou,Peifen Yao,Caifang Gao,Jinchao Wei,Carolina Oi Lam Ung,Shengpeng Wang,Zhangfeng Zhong,Yitao Wang +16 more
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Yuyu Zhu,Zijun Ouyang,Haojie Du,Mei Jing Wang,Jiaojiao Wang,Haiyan Sun,Ling-dong Kong,Qiang Xu,Hongyue Ma,Yang Sun +9 more
TL;DR: Wang et al. as mentioned in this paper reviewed the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introducing the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients.
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Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope.
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