PMID- 35955957
OWN - NLM
STAT- MEDLINE
DCOM- 20220815
LR  - 20220815
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 15
DP  - 2022 Aug 8
TI  - Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum 
      Stress-Mitochondrial Apoptotic and Autophagic Signaling Pathway.
LID - 10.3390/ijms23158813 [doi]
LID - 8813
AB  - Oral squamous cell carcinoma (OSCC) affects tens of thousands of people 
      worldwide. Despite advances in cancer treatment, the 5-year survival rate of 
      patients with late-stage OSCC is low at 50-60%. Therefore, the development of 
      anti-OSCC therapy is necessary. We evaluated the effects of marine-derived 
      triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B 
      dose-dependently decreased the viability of both cell lines, with a significant 
      reduction in OC2 cells at >/=0.1 microM at 24 and 48 h, and in SCC4 cells at >/=1 microM at 
      24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling 
      (TUNEL)-positive cells were significantly observed at 20 microM of stellettin B at 48 
      h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) 
      polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by 
      stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were 
      increased, whereas p62 was decreased. At 20 microM at 48 h, the expression levels of 
      the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were 
      significantly increased and mitogen-activated protein kinase (MAPK) signaling 
      pathways were activated. Further investigation using the autophagy inhibitor 
      3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell 
      death and autophagy. Overall, our findings show that stellettin B induces the ER 
      stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of 
      OSCC cells.
FAU - Kuo, Tsu-Jen
AU  - Kuo TJ
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 80424, Taiwan.
AD  - School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan.
AD  - Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, 
      Taiwan.
FAU - Jean, Yen-Hsuan
AU  - Jean YH
AD  - Section of Orthopedics, Department of Surgery, Antai Medical Care Corporation 
      Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan.
FAU - Shih, Po-Chang
AU  - Shih PC
AUID- ORCID: 0000-0002-6124-5090
AD  - Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung 83301, Taiwan.
FAU - Cheng, Shu-Yu
AU  - Cheng SY
AD  - Department of Environmental Protection, Green Technology Research Institute, CPC 
      Corporation, No. 2, Zuonan Rd., Nan-Tzu District, Kaohsiung 81126, Taiwan.
FAU - Kuo, Hsiao-Mei
AU  - Kuo HM
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 80424, Taiwan.
FAU - Lee, Yi-Ting
AU  - Lee YT
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 80424, Taiwan.
FAU - Lai, Yu-Cheng
AU  - Lai YC
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 80424, Taiwan.
AD  - Department of Orthopedics, Asia University Hospital, Taichung 41354, Taiwan.
FAU - Tseng, Chung-Chih
AU  - Tseng CC
AUID- ORCID: 0000-0002-5791-5928
AD  - Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, 
      Taiwan.
AD  - Institute of Medical Science and Technology, National Sun Yat-sen University, 
      Kaohsiung 80424, Taiwan.
FAU - Chen, Wu-Fu
AU  - Chen WF
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 80424, Taiwan.
AD  - Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung 83301, Taiwan.
FAU - Wen, Zhi-Hong
AU  - Wen ZH
AUID- ORCID: 0000-0003-4411-044X
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 80424, Taiwan.
LA  - eng
GR  - 109-2314-B-182A-080-MY2/Ministry of Science and Technology of Taiwan/
GR  - 108-2313-B-110-001-MY3/Ministry of Science and Technology of Taiwan/
GR  - VGHKS109-119/Kaohsiung Veterans General Hospital/
GR  - CMRPG8K1402/Chang Gung Memorial Hospital/
PT  - Journal Article
DEP - 20220808
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Triterpenes)
RN  - 0 (stellettin B)
SB  - IM
MH  - Apoptosis
MH  - Autophagy
MH  - *Carcinoma, Squamous Cell/drug therapy
MH  - Endoplasmic Reticulum Stress
MH  - Humans
MH  - *Mouth Neoplasms/drug therapy
MH  - Signal Transduction
MH  - *Triterpenes/pharmacology
PMC - PMC9368952
OTO - NOTNLM
OT  - BiP/GRP78
OT  - ER stress
OT  - autophagy
OT  - mitochondrial stress
OT  - stellettin B
COIS- The authors declare no conflict of interest.
EDAT- 2022/08/13 06:00
MHDA- 2022/08/16 06:00
PMCR- 2022/08/08
CRDT- 2022/08/12 01:14
PHST- 2022/07/12 00:00 [received]
PHST- 2022/08/03 00:00 [revised]
PHST- 2022/08/05 00:00 [accepted]
PHST- 2022/08/12 01:14 [entrez]
PHST- 2022/08/13 06:00 [pubmed]
PHST- 2022/08/16 06:00 [medline]
PHST- 2022/08/08 00:00 [pmc-release]
AID - ijms23158813 [pii]
AID - ijms-23-08813 [pii]
AID - 10.3390/ijms23158813 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Aug 8;23(15):8813. doi: 10.3390/ijms23158813.