PMID- 27465776
OWN - NLM
STAT- MEDLINE
DCOM- 20180212
LR  - 20180212
IS  - 1600-0714 (Electronic)
IS  - 0904-2512 (Linking)
VI  - 46
IP  - 3
DP  - 2017 Mar
TI  - Synergistic effect of honokiol and 5-fluorouracil on apoptosis of oral squamous 
      cell carcinoma cells.
PG  - 201-207
LID - 10.1111/jop.12481 [doi]
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is an essential chemotherapeutic agent for oral 
      squamous cell carcinoma (OSCC). However, toxic side effects have limited its role 
      in OSCC therapy. The aim of this study was to explore whether combination therapy 
      with 5-FU and honokiol (HNK), a small natural organic molecule shown to induce 
      apoptosis in OSCC cells, could enhance the anticancer activity of 5-FU without 
      notably increasing its toxicity. METHODS: 5-FU and/or HNK were used to treat OSCC 
      cells both in vitro and in vivo. The therapeutic effect and underlying mechanisms 
      were evaluated by cell viability assay, flow cytometry, OSCC xenograft mouse 
      model, and Western blot. Tumor tissue apoptosis was detected by terminal 
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Toxicity was 
      assessed following hematoxylin and eosin staining. RESULTS: Exposure to HNK + 
      5-FU produced a synergistic cytotoxic effect on OSCC cells. Both HNK and 5-FU 
      could induce apoptosis through the mitochondria-mediated intrinsic pathway, and 
      their specific signaling pathways were different. In the mouse OSCC xenograft 
      model, treatment with 5-FU + HNK substantively retarded tumor growth, as compared 
      to treatment with either drug individually. TUNEL analysis further confirmed that 
      the superior in vivo antitumor efficacy of 5-FU + HNK was associated with 
      enhanced stimulation of cell apoptosis. Notably, HNK did not increase the 
      toxicity of 5-FU. CONCLUSION: These findings suggest that HNK and 5-FU exert a 
      synergistic therapeutic effect on OSCC by inducing apoptosis. HNK might thus 
      enhance the clinical therapeutic efficacy of 5-FU without increasing its 
      toxicity.
CI  - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Ji, Ning
AU  - Ji N
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Jiang, Lu
AU  - Jiang L
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Deng, Peng
AU  - Deng P
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Xu, Hao
AU  - Xu H
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Chen, Fangman
AU  - Chen F
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Liu, Jinli
AU  - Liu J
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Li, Jing
AU  - Li J
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Liao, Ga
AU  - Liao G
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Zeng, Xin
AU  - Zeng X
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Lin, Yuchun
AU  - Lin Y
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Feng, Mingye
AU  - Feng M
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Li, Longjiang
AU  - Li L
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Chen, Qianming
AU  - Chen Q
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu, Sichuan, China.
LA  - eng
PT  - Journal Article
DEP - 20160728
PL  - Denmark
TA  - J Oral Pathol Med
JT  - Journal of oral pathology & medicine : official publication of the International 
      Association of Oral Pathologists and the American Academy of Oral Pathology
JID - 8911934
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Lignans)
RN  - 11513CCO0N (honokiol)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Biphenyl Compounds/*pharmacology/therapeutic use
MH  - Carcinoma, Squamous Cell/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Drug Synergism
MH  - Female
MH  - Fluorouracil/*pharmacology/therapeutic use
MH  - Humans
MH  - Lignans/*pharmacology/therapeutic use
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mouth Neoplasms/*drug therapy/pathology
OTO - NOTNLM
OT  - 5-fluorouracil
OT  - apoptosis
OT  - honokiol
OT  - oral squamous cell carcinoma
OT  - synergistic effect
EDAT- 2016/07/29 06:00
MHDA- 2018/02/13 06:00
CRDT- 2016/07/29 06:00
PHST- 2016/07/01 00:00 [accepted]
PHST- 2016/07/29 06:00 [pubmed]
PHST- 2018/02/13 06:00 [medline]
PHST- 2016/07/29 06:00 [entrez]
AID - 10.1111/jop.12481 [doi]
PST - ppublish
SO  - J Oral Pathol Med. 2017 Mar;46(3):201-207. doi: 10.1111/jop.12481. Epub 2016 Jul 
      28.