title: A novel therapeutic approach against B-cell non-Hodgkin's lymphoma through co-inhibition of Hedgehog signaling pathway and autophagy.
abstract: B-cell non-Hodgkin's lymphoma (B-NHL) is one of the most common types of cancer in the world, with half of the patients dying due to the resistance or tolerance against the treatment. Thus, a novel therapeutic approach for B-NHL treatment was urgently needed. In this study, we investigated the potential of co-inhibition of Hedgehog signaling pathway (Hh) and autophagy in B-NHL therapy. We reported that vismodegib, an inhibitor of Hedgehog signaling pathway, could block the Hh pathway and induce cytotoxicity and apoptosis in B-NHL Raji cells. During this process, autophagy was activated as a response to Hh inhibition. Importantly, inhibition of autophagy potentiated the cytotoxicity and caspase 3-dependent apoptosis induced by vismodegib in B-NHL cells. Furthermore, clearance of ROS generation caused a decreased activity of autophagy and attenuated cytotoxicity in vismodegib-treated cells, while inhibition of autophagy accelerated the formation of ROS, indicating that ROS was required for vismodegib-induced autophagy and cytotoxicity in B-NHL cells. Our results demonstrated that co-inhibition of Hh pathway and autophagy could potently kill B-NHL cells and highlighted a novel approach for B-NHL therapy by co-inhibition of Hh pathway and cytoprotective autophagy.
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China.|Bioinformatics and Drug Design Group, Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore.
authors.forename: Xian
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Shaofei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Instrumental Analysis Center, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Instrumental Analysis Center, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Zhonglian
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. Meixiaobin@medmail.com.cn.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203, China. dianwenju@fudan.edu.cn.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; C538724:HhAntag691; D009363:Neoplasm Proteins; D011725:Pyridines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species
keywords: Apoptosis; Autophagy; B-NHL; Hedgehog pathway; Vismodegib