title: Pulsatilla Saponin D Inhibits Autophagic Flux and Synergistically Enhances the Anticancer Activity of Chemotherapeutic Agents Against HeLa Cells.
abstract: Pulsatilla saponin D (SB365), a saponin isolated from rhizoma of Pulsatilla chinensis (Bunge) Regel, exhibited anticancer activities in various cancer types. In the present study, we identified that SB365 was a potent inhibitor of autophagic flux in several cancer cell lines. SB365 induced a robust accumulation of autophagosomes as evidenced by monodansylaervarine (MDC) staining and increased protein levels of LC3-II. However, SB365 caused the accumulation of p62, a substrate that should be degraded through the autophagy-lysosomal pathway. These results indicated that SB365 was an inducer of autophagosome formation, but an inhibitor of autophagic flux. Interestingly, we found that SB365 synergistically enhanced the anticancer activity of chemotherapeutic agents against cervical cancer HeLa cells. Furthermore, our study demonstrated that SB365 increased the phosphorylation of ERK and inhibited the phosphorylation of mTOR and p70S6K, suggesting that their roles in the effects of SB365 on autophagy. These results suggest that SB365 could be a promising adjuvant anticancer agent.
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Bao
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Jia
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Borong
authors.initials: B
authors.lastname: Huang
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wan
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D001343:Autophagy / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D031946:Pulsatilla / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; C000601508:Pulsatilla saponin D; D016601:RNA-Binding Proteins; D012503:Saponins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Anticancer; Autophagic Flux; HeLa Cells; Pulsatilla Saponin D