PMID- 32470830
OWN - NLM
STAT- MEDLINE
DCOM- 20201029
LR  - 20201029
IS  - 1879-1506 (Electronic)
IS  - 0003-9969 (Linking)
VI  - 116
DP  - 2020 Aug
TI  - Isobutyrylshikonin has a potentially stronger cytotoxic effect in oral cancer 
      cells than its analogue shikonin in vitro.
PG  - 104774
LID - S0003-9969(20)30152-7 [pii]
LID - 10.1016/j.archoralbio.2020.104774 [doi]
AB  - OBJECTIVES: The aim of the present study was to identify the anticancer effects 
      and the mechanisms of action of shikonin and its analogue isobutyrylshikonin in 
      oral squamous carcinoma cells. DESIGNS: The cytotoxic effects of 
      isobutyrylshikonin and shikonin in Ca9-22 and SCC-25 cells were analyzed using 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow 
      cytometry analysis of Annexin V/Propidium Iodide (PI) staining, western blot 
      analysis and immunohistochemistry. RESULTS: Treatment with both 
      isobutyrylshikonin and shikonin induced dose- and time-dependent apoptotic cell 
      death in Ca9-22 cells, although the IC(50) of isobutyrylshikonin was less than 
      that of shikonin. The induction of apoptosis by both isobutyrylshikonin and 
      shikonin was accompanied by activation of caspase-8, -9, -3, and PARP, loss of 
      mitochondrial trans-membrane potential, and release of cytochrome c from the 
      mitochondria. ROS mediated the apoptosis induced by isobutyrylshikonin and 
      shikonin, indicating that ROS may play a critical role in the distinctive 
      cytotoxic effects of isobutyrylshikonin and shikonin in Ca9-22. 
      Isobutyrylshikonin showed a similar cytotoxic effect in SCC-25 cells at 
      concentrations showing the effects in Ca9 cells, but not in human normal 
      keratinocyte cells. Although there is no biological difference between 
      isobutyrylshikonin and shikonin, isobutyrylshikonin exerts the same cytotoxic 
      effect at a concentration 6 times lower than shikonin. CONCLUSIONS: The present 
      study suggest that isobutyrylshikonin may be a more potent chemotherapeutic agent 
      against oral cancer cells than shikonin. In addition, our data exhibit that both 
      isobutyrylshikonin and shikonin induce caspase-dependent apoptosis via the 
      mitochondrial pathway through accumulation of ROS in oral squamous carcinoma 
      cells.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Park, Dae-Gun
AU  - Park DG
AD  - Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan 
      National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea.
FAU - Kim, Da Jeong
AU  - Kim DJ
AD  - Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan 
      National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea.
FAU - Woo, Bok Hee
AU  - Woo BH
AD  - Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan 
      National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea.
FAU - Kim, Hye Jung
AU  - Kim HJ
AD  - Periodontal Disease Signaling Network Research Center, Dental & Life Science 
      Institute, Pusan National University, 49 Busandaehak-Ro, Yangsan 626-870, South 
      Korea.
FAU - Choi, Young Whan
AU  - Choi YW
AD  - Department of Horticultural Bioscience, Pusan National University, Samnangjin-Ro 
      1268-50, Samnangjin-eup, Miryang 627-706, South Korea.
FAU - Park, Hae Ryoun
AU  - Park HR
AD  - Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan 
      National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea; Periodontal 
      Disease Signaling Network Research Center, Dental & Life Science Institute, Pusan 
      National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea. Electronic 
      address: parkhr@pusan.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20200520
PL  - England
TA  - Arch Oral Biol
JT  - Archives of oral biology
JID - 0116711
RN  - 0 (Naphthoquinones)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (isobutyrylshikonin)
RN  - 3IK6592UBW (shikonin)
SB  - IM
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Humans
MH  - Membrane Potential, Mitochondrial
MH  - *Mouth Neoplasms/drug therapy
MH  - *Naphthoquinones/pharmacology/toxicity
MH  - Reactive Oxygen Species
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Apoptosis
OT  - Isobutyrylshikonin
OT  - Oral cancer
OT  - Oral squamous cell carcinoma
OT  - Reactive oxygen species
OT  - Shikonin
EDAT- 2020/05/30 06:00
MHDA- 2020/10/30 06:00
CRDT- 2020/05/30 06:00
PHST- 2020/02/07 00:00 [received]
PHST- 2020/05/14 00:00 [revised]
PHST- 2020/05/16 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2020/10/30 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
AID - S0003-9969(20)30152-7 [pii]
AID - 10.1016/j.archoralbio.2020.104774 [doi]
PST - ppublish
SO  - Arch Oral Biol. 2020 Aug;116:104774. doi: 10.1016/j.archoralbio.2020.104774. Epub 
      2020 May 20.