AstragalosideII inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells.
Inhibition of autophagy has been daily served as a promising anti-cancer treatment strategies. AstragalosideII (ASII), a main compound isolated from traditional Chinese medicine Radix Astragali, has been demonstrated to inhibit autophagy and reverse multidrug resistance in human hepatic cancer cells Bel-7402/5-FU. In this study, we inspected the function and mechanisms of ASII and cisplatin on autophagy in human cancer cells, and assessed the effect of ASII on cisplatin-induced apoptosis. We found ASII increased LC3II protein level, p62 protein level and GFP-LC3 puncta accumulation in human cancer cells. Furthermore, we found that ASII downregulated the expression of lysosomal cathepsinB/L (CTSB/L) in EBSS medium and affected the lysosomal acidification. Finally, we demonstrated that cisplatin induced protective autophagy which was involved of PI3K/Akt/mTOR pathway. Moreover, ASII in conjunction with cisplatin significant reduced cell viability, arrested in S phase and increased apoptosis. In conclusion, these findings suggested that ASII served as autophagy inhibitor which restored chemosensitivity of anticancer agent cisplatin and enhanced tumor cell death.
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China; Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230032 Anhui, China.
Cui
C
Yang
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China; Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230032 Anhui, China.
Chao
C
Wu
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China; Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230032 Anhui, China. Electronic address: xudujuan6365@163.com.
Dujuan
D
Xu
Anhui Provincial Hospital, Hefei 230032, Anhui, China.
Meng
M
Wang
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China; Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230032 Anhui, China.
Quan
Q
Xia
D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D002945:Cisplatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012503:Saponins; D058570:TOR Serine-Threonine Kinases; C580601:astragaloside II; C546842:MTOR protein, human
Apoptosis; AstragalosideII; Autophagy; Cisplatin; Sensitization