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: Yulin Zhang, Jiaolin Bao, Kai Wang, Xuejing Jia, Chao Zhang, Borong Huang, Meiwan Chen, Jian-Bo Wan, Huanxing Su, Yitao Wang, Chengwei He
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 43 Issue 8 Pg. 1657-70 ( 2015) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 26732119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• P62 protein, human
• Pulsatilla saponin D
• RNA-Binding Proteins
• Saponins
• MTOR protein, human
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• Extracellular Signal-Regulated MAP Kinases

Topics

• Antineoplastic Agents, Phytogenic
• Autophagy (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• HeLa Cells
• Humans
• Microtubule-Associated Proteins (metabolism)
• Phosphorylation (drug effects)
• Phytotherapy
• Pulsatilla (chemistry)
• RNA-Binding Proteins (metabolism)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Saponins (isolation & purification, pharmacology)
• TOR Serine-Threonine Kinases (metabolism)
• Uterine Cervical Neoplasms (drug therapy, genetics, pathology)