PMID- 32810561
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20231213
IS  - 1872-8006 (Electronic)
IS  - 0304-4165 (Linking)
VI  - 1864
IP  - 12
DP  - 2020 Dec
TI  - Synchrotron FTIR microspectroscopy revealed apoptosis-induced biomolecular 
      changes of cholangiocarcinoma cells treated with ursolic acid.
PG  - 129708
LID - S0304-4165(20)30220-8 [pii]
LID - 10.1016/j.bbagen.2020.129708 [doi]
AB  - BACKGROUND: Ursolic acid (UA) is a natural triterpenoid which possesses 
      anti-cancer activity. However, little is known regarding the activity and 
      molecular mechanism of UA in cholangiocarcinoma (CCA). Thus, we investigated the 
      effects of UA on growth inhibition and apoptosis induction through biomolecular 
      changes in KKU-213 and KKU-055 CCA cell lines. METHODS: The anti-proliferative 
      effect of UA against CCA cells was evaluated using SRB assay. Changes in 
      biomolecules were assessed by SR-FTIR microspectroscopy combined with PCA and 
      conventional methods (i.e., Annexin V-FITC/PI staining for lipid alteration and 
      apoptosis induction; Western blot analysis and caspase-3/7 activity assay for 
      apoptotic protein detection). RESULTS: UA suppressed the proliferation of CCA 
      cells in a dose- and time-dependent manner. SR-FTIR data revealed a significant 
      alteration in lipids attributable to changes in apoptotic cell membranes, 
      confirmed by Annexin V-FITC/PI staining. SR-FTIR data showed that UA promoted 
      changes in the protein secondary structure. Elevated expression of Bax and 
      decreased expression of Bcl-2 and survivin/BIRC5 along with augmented caspase-3/7 
      activity supported alterations in apoptosis-related proteins. CONCLUSIONS: 
      SR-FTIR microspectroscopy was successfully used as a label-free technique to 
      monitor apoptosis-induced biomolecular changes in UA-treated CCA cells. UA 
      exerted the cytotoxic and apoptotic activities in CCA cells through alterations 
      in membrane lipids and apoptotic proteins. UA could be a potential anti-CCA 
      candidate and a chemical starting point for the discovery of novel anti-cancer 
      agents. SIGNIFICANCE: Our present study showed the first evidence that UA 
      exhibited the anti-proliferative and pro-apoptotic activities toward CCA cells 
      through changes in biomolecules, notably lipids and proteins.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Maphanao, Pornpattra
AU  - Maphanao P
AD  - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 
      40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 
      Khon Kaen 40002, Thailand.
FAU - Thanan, Raynoo
AU  - Thanan R
AD  - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 
      40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 
      Khon Kaen 40002, Thailand.
FAU - Loilome, Watcharin
AU  - Loilome W
AD  - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 
      40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 
      Khon Kaen 40002, Thailand.
FAU - Chio-Srichan, Sirinart
AU  - Chio-Srichan S
AD  - Synchrotron Light Research Institute (Public Organization), Nakhon Ratchasima, 
      30000, Thailand.
FAU - Wongwattanakul, Molin
AU  - Wongwattanakul M
AD  - Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, 
      Thailand; Center for Innovation and Standard for Medical Technology and Physical 
      Therapy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 
      40002, Thailand.
FAU - Sakonsinsiri, Chadamas
AU  - Sakonsinsiri C
AD  - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 
      40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 
      Khon Kaen 40002, Thailand. Electronic address: schadamas@kku.ac.th.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200815
PL  - Netherlands
TA  - Biochim Biophys Acta Gen Subj
JT  - Biochimica et biophysica acta. General subjects
JID - 101731726
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Triterpenes)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Bile Duct Neoplasms/chemistry/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Cholangiocarcinoma/chemistry/*drug therapy/pathology
MH  - Humans
MH  - Spectroscopy, Fourier Transform Infrared/instrumentation
MH  - Synchrotrons/instrumentation
MH  - Triterpenes/*pharmacology
MH  - Ursolic Acid
OTO - NOTNLM
OT  - Apoptosis
OT  - Cholangiocarcinoma
OT  - Fourier transform infrared
OT  - Microspectroscopy
OT  - Synchrotron
OT  - Ursolic acid
COIS- Declaration of Competing Interest The authors disclose no conflicts of interest.
EDAT- 2020/08/19 06:00
MHDA- 2021/01/05 06:00
CRDT- 2020/08/19 06:00
PHST- 2020/04/30 00:00 [received]
PHST- 2020/07/23 00:00 [revised]
PHST- 2020/08/10 00:00 [accepted]
PHST- 2020/08/19 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/08/19 06:00 [entrez]
AID - S0304-4165(20)30220-8 [pii]
AID - 10.1016/j.bbagen.2020.129708 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Gen Subj. 2020 Dec;1864(12):129708. doi: 
      10.1016/j.bbagen.2020.129708. Epub 2020 Aug 15.