PMID- 30553871
OWN - NLM
STAT- MEDLINE
DCOM- 20190301
LR  - 20190301
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 218
DP  - 2019 Feb 1
TI  - Endoplasmic reticulum stress triggered by Soyasapogenol B promotes apoptosis and 
      autophagy in colorectal cancer.
PG  - 16-24
LID - S0024-3205(18)30805-1 [pii]
LID - 10.1016/j.lfs.2018.12.023 [doi]
AB  - AIM: Colorectal cancer (CRC) is a common human malignancy which accounts for 
      600,000 deaths annually at the global level. Soyasapogenol B (Soy B), an 
      ingredient of soybean, has been found to exert anti-proliferative activities in 
      vitro in human breast cancer cells. The current study aimed to evaluate the 
      efficacy of Soy B in suppressing CRC. METHODS AND MATERIALS: The effect of Soy B 
      on cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. The 
      effect of Soy B on cell proliferation was determined using colony formation 
      assay. The percentage of apoptotic cells was determined by the TUNEL assay and 
      flow cytometry following Annexin V-FITC/Propidium Iodide (PI) double staining. 
      JC-1 staining was performed to examine the change in mitochondrial membrane 
      potential. Autophagy was examined by acridine orange staining and mRFP-GFP-LC3 
      adenovirus transfection. Caspase-12 activities were determined by ELISA kit. 
      Western blotting was used to determine the expression of relevant proteins. To 
      investigate the role of autophagy in the pro-death and pro-apoptotic activities 
      of Soy B, autophagy inhibitors Bafilomycin A1 (Baf-A1) and Atg5 siRNA were 
      utilized. TUDCA and CHOP shRNA were utilized to block ER stress. Moreover, a CRC 
      xenograft murine model was used to analyze the therapeutic efficacy of Soy B in 
      vivo. KEY FINDINGS: Soy B treatment decreased the number of viable cells and 
      colonies formed in CRC cell lines. Moreover, Soy B treatment promoted the 
      apoptotic cell death via the intrinsic pathway and autophagy which positively 
      contributed to cell death and apoptosis. In addition, our results showed that ER 
      stress, triggered by Soy B, mediated apoptosis and autophagy. In vivo results 
      revealed that Soy B could suppress tumor growth, which was associated with 
      increased ER stress, accompanied with apoptosis and autophagy induction. 
      SIGNIFICANCE: Soy B was able to promote cell death in vitro and in vivo. Our 
      findings highlight the possibility of utilizing Soy B as a chemotherapeutic agent 
      to prevent and treat CRC.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Wang, Luping
AU  - Wang L
AD  - The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
FAU - Yun, Lu
AU  - Yun L
AD  - Qingdao Central Hospital, Qingdao, Shandong, China.
FAU - Wang, Xiaojun
AU  - Wang X
AD  - The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
FAU - Sha, Liying
AU  - Sha L
AD  - The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
FAU - Wang, Luning
AU  - Wang L
AD  - The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
FAU - Sui, Yingying
AU  - Sui Y
AD  - The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. 
      Electronic address: huizhangqyfu@163.com.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20181214
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Saponins)
RN  - 1EZ10D7E2F (soyasapogenol B)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
SB  - IM
RIN - Life Sci. 2020 Aug 1;254:117825. PMID: 32482464
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - *Autophagy
MH  - Cell Proliferation/drug effects
MH  - Colorectal Neoplasms/drug therapy/*pathology
MH  - *Endoplasmic Reticulum Stress
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Oleanolic Acid/*analogs & derivatives/pharmacology
MH  - Saponins/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Colorectal cancer
OT  - Endoplasmic reticulum stress
OT  - Soy B
EDAT- 2018/12/17 06:00
MHDA- 2019/03/02 06:00
CRDT- 2018/12/17 06:00
PHST- 2018/11/08 00:00 [received]
PHST- 2018/12/06 00:00 [revised]
PHST- 2018/12/13 00:00 [accepted]
PHST- 2018/12/17 06:00 [pubmed]
PHST- 2019/03/02 06:00 [medline]
PHST- 2018/12/17 06:00 [entrez]
AID - S0024-3205(18)30805-1 [pii]
AID - 10.1016/j.lfs.2018.12.023 [doi]
PST - ppublish
SO  - Life Sci. 2019 Feb 1;218:16-24. doi: 10.1016/j.lfs.2018.12.023. Epub 2018 Dec 14.