PMID- 26969378
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20211203
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 23
IP  - 3
DP  - 2016 Mar 15
TI  - Diosgenin induces ROS-dependent autophagy and cytotoxicity via mTOR signaling 
      pathway in chronic myeloid leukemia cells.
PG  - 243-52
LID - S0944-7113(16)00028-3 [pii]
LID - 10.1016/j.phymed.2016.01.010 [doi]
AB  - BACKGROUND: Diosgenin, a steroidal saponin isolated from legumes and yams, has 
      been confirmed to possess potent anticancer effect on multifarious tumors 
      including chronic myeloid leukemia (CML). PURPOSE: We aimed to further determine 
      the anti-cancer activity of diosgenin and its mechanisms in CML cells. METHODS: 
      The cell vitality was detected by MTT assay. Autophagic flux and reactive oxygen 
      species (ROS) production were analyzed by laser scanning confocal microscope. 
      Apoptosis was observed by flow cytometry. All proteins expression was examined by 
      western blotting. RESULTS: Autophagy induction was demonstrated by examination of 
      autophagic flux including autophagosomes accumulation, autophagosome-lysosome 
      fusion and degradation of autophagosomes. Moreover, blocking autophagy with 
      inhibitor chloroquine (CQ) and 3-methyladenine (3-MA), enhanced diosgenin-induced 
      apoptosis, indicating the protective effect of autophagy in diosgenin-treated CML 
      cells. Further study suggested that diosgenin-induced autophagy and cytotoxicity 
      were accompanied by reactive oxygen species (ROS) generation and mammalian target 
      of rapamycin (mTOR) signaling pathway inhibition. N-acetyl-L-cysteine (NAC) 
      administration, a scavenger agent of ROS, could down-regulate diosgenin-induced 
      autophagy via reversion of mTOR pathway inhibition. CONCLUSION: These results 
      indicate that diosgenin obviously generates ROS and this oxidative pressure not 
      only produces cytotoxic effect on CML cells but also induces autophagy. What's 
      more, autophagy functions as a cytoprotective mechanism to overcome cytotoxicity 
      of diosgenin in tumor cells and inhibition of autophagy can enhance the anti-CML 
      activity of diosgenin.
CI  - Copyright (c) 2016 Elsevier GmbH. All rights reserved.
FAU - Jiang, Shanshan
AU  - Jiang S
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Fan, Jiajun
AU  - Fan J
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Ju, Dianwen
AU  - Ju D
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Feng, Meiqing
AU  - Feng M
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Li, Jiyang
AU  - Li J
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Guan, Zhong-Bin
AU  - Guan ZB
AD  - Shanghai Institute For Food And Drug Control, Shanghai, China.
FAU - An, Duopeng
AU  - An D
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Wang, Xin
AU  - Wang X
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China.
FAU - Ye, Li
AU  - Ye L
AD  - Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of 
      Education, School of Pharmacy, Fudan University, Shanghai, China. Electronic 
      address: yelil@fudan.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160209
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - K49P2K8WLX (Diosgenin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Cell Line, Tumor
MH  - Diosgenin/*pharmacology
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology
MH  - Mice
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Chronic myeloid leukemia
OT  - Cytotoxicity
OT  - Diosgenin
OT  - Reactive oxygen species
EDAT- 2016/03/13 06:00
MHDA- 2016/09/23 06:00
CRDT- 2016/03/13 06:00
PHST- 2015/12/07 00:00 [received]
PHST- 2016/01/18 00:00 [revised]
PHST- 2016/01/26 00:00 [accepted]
PHST- 2016/03/13 06:00 [entrez]
PHST- 2016/03/13 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
AID - S0944-7113(16)00028-3 [pii]
AID - 10.1016/j.phymed.2016.01.010 [doi]
PST - ppublish
SO  - Phytomedicine. 2016 Mar 15;23(3):243-52. doi: 10.1016/j.phymed.2016.01.010. Epub 
      2016 Feb 9.