PMID- 28197628
OWN - NLM
STAT- MEDLINE
DCOM- 20170613
LR  - 20211204
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 50
IP  - 3
DP  - 2017 Mar
TI  - Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral 
      cancer CAR cells: A key role of AMPK and Akt/mTOR signaling.
PG  - 873-882
LID - 10.3892/ijo.2017.3866 [doi]
AB  - Resveratrol is known to be an effective chemo-preventive phytochemical against 
      multiple tumor cells. However, the increasing drug resistance avoids the cancer 
      treatment in oral cavity cancer. In this study, we investigated the oral 
      antitumor activity of resveratrol and its mechanism in cisplatin-resistant human 
      oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely 
      low toxicity in normal oral cells and provoked autophagic cell death to form 
      acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by 
      acridine orange (AO) and monodansylcadaverine (MDC) staining. Either DNA 
      fragmentation or DNA condensation occurred in resveratrol-triggered CAR cell 
      apoptosis. These inhibitors of PI3K class III (3-MA) and AMP-activated protein 
      kinase (AMPK) (compound c) suppressed the autophagic vesicle formation, LC3-II 
      protein levels and autophagy induced by resveratrol. The pan-caspase inhibitor 
      Z-VAD-FMK attenuated resveratrol-triggered cleaved caspase-9, cleaved caspase-3 
      and cell apoptosis. Resveratrol also enhanced phosphorylation of AMPK and 
      regulated autophagy- and pro-apoptosis-related signals in resveratrol-treated CAR 
      cells. Importantly, resveratrol also stimulated the autophagic mRNA gene 
      expression, including Atg5, Atg12, Beclin-1 and LC3-II in CAR cells. Overall, our 
      findings indicate that resveratrol is likely to induce autophagic and apoptotic 
      death in drug-resistant oral cancer cells and might become a new approach for 
      oral cancer treatment in the near future.
FAU - Chang, Chao-Hsiang
AU  - Chang CH
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, 
      Taiwan, R.O.C.
FAU - Lee, Chao-Ying
AU  - Lee CY
AD  - School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C.
FAU - Lu, Chi-Cheng
AU  - Lu CC
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung 404, Taiwan, R.O.C.
FAU - Tsai, Fuu-Jen
AU  - Tsai FJ
AD  - Human Genetic Center, China Medical University Hospital, Taichung 404, Taiwan, 
      R.O.C.
FAU - Hsu, Yuan-Man
AU  - Hsu YM
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung 404, Taiwan, R.O.C.
FAU - Tsao, Je-Wei
AU  - Tsao JW
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung 404, Taiwan, R.O.C.
FAU - Juan, Yu-Ning
AU  - Juan YN
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung 404, Taiwan, R.O.C.
FAU - Chiu, Hong-Yi
AU  - Chiu HY
AD  - Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, 
      R.O.C.
FAU - Yang, Jai-Sing
AU  - Yang JS
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung 404, Taiwan, R.O.C.
FAU - Wang, Ching-Chiung
AU  - Wang CC
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, 
      Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
DEP - 20170130
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (ATG12 protein, human)
RN  - 0 (ATG5 protein, human)
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Autophagy-Related Protein 12)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Beclin-1)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Stilbenes)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - Q20Q21Q62J (Cisplatin)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 12/genetics
MH  - Autophagy-Related Protein 5/genetics
MH  - Beclin-1/genetics
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - Cell Line, Tumor
MH  - Cisplatin/pharmacology
MH  - DNA Fragmentation/drug effects
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Microtubule-Associated Proteins/genetics
MH  - Mouth Neoplasms/*pathology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA, Messenger/genetics
MH  - Resveratrol
MH  - Signal Transduction/drug effects
MH  - Stilbenes/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2017/02/16 06:00
MHDA- 2017/06/14 06:00
CRDT- 2017/02/16 06:00
PHST- 2016/12/01 00:00 [received]
PHST- 2017/01/23 00:00 [accepted]
PHST- 2017/02/16 06:00 [pubmed]
PHST- 2017/06/14 06:00 [medline]
PHST- 2017/02/16 06:00 [entrez]
AID - 10.3892/ijo.2017.3866 [doi]
PST - ppublish
SO  - Int J Oncol. 2017 Mar;50(3):873-882. doi: 10.3892/ijo.2017.3866. Epub 2017 Jan 
      30.