PMID- 32407876
OWN - NLM
STAT- MEDLINE
DCOM- 20210312
LR  - 20210312
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 67
DP  - 2020 Sep
TI  - Cetuximab enhances oridonin-induced apoptosis through mitochondrial pathway and 
      endoplasmic reticulum stress in laryngeal squamous cell carcinoma cells.
PG  - 104885
LID - S0887-2333(20)30070-9 [pii]
LID - 10.1016/j.tiv.2020.104885 [doi]
AB  - Cetuximab plus oridonin showed a synergistic way to kill laryngeal squamous cell 
      carcinoma (LSCC), as been reported previously. The present work further 
      mechanistically extended action of the synergistic effects of combination 
      treatment. Firstly, two LSCC cells displayed higher sensitivity to oridonin, 
      whereas both low EGFR expression tumor cells and EGFR knockdown LSCC cells were 
      less sensitive to oridonin. Next, cetuximab/oridonin significantly enhanced the 
      mitochondrial apoptosis through NF-kappaB. Meanwhile, PI3K/Akt and JAK2/STAT3 
      pathways are associated with the nucleus translocation of NF-kappaB by combination 
      treatment. Additionally, cetuximab enhanced oridonin-promoted ER stress-related 
      apoptosis. Interestingly, both ER stress and mitochondrial apoptosis by 
      combination treatment are abrogated by ROS scavenger. Furthermore, 
      oridonin/cetuximab induced ROS production after 1.5 h, followed by G2/M arrest 
      and apoptosis, indicating that ROS generation might be an early and key event. 
      Taken together, cetuximab enhances oridonin-induced ER stress and mitochondrial 
      apoptotic pathway, which contributes to the synergistic antitumor effects of 
      cetuximab/oridonin.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Kang, Ning
AU  - Kang N
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, Tianjin 301617, PR China.
FAU - Cao, Shijie
AU  - Cao S
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin 301617, PR China.
FAU - Jiang, Benke
AU  - Jiang B
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, Tianjin 301617, PR China; Faculty of Life Sciences and Biological 
      Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, Tianjin 301617, PR China.
FAU - Donkor, Paul Owusu
AU  - Donkor PO
AD  - School of Pharmacy, University of Ghana, Korle Bu, Accra, P.O. Box 52, Ghana.
FAU - Zhu, Yan
AU  - Zhu Y
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin 301617, PR China.
FAU - Qiu, Feng
AU  - Qiu F
AD  - School of Chinese Materia Medica, Tianjin University of Traditional Chinese 
      Medicine, Tianjin 301617, PR China. Electronic address: fengqiu20070118@163.com.
FAU - Gao, Xiumei
AU  - Gao X
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin 301617, PR China. Electronic address: 
      gaoxiumei@tjutcm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200512
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Diterpenes, Kaurane)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0APJ98UCLQ (oridonin)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Antineoplastic Agents, Immunological/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Squamous Cell/*drug therapy
MH  - Cell Line, Tumor
MH  - Cetuximab/*pharmacology
MH  - Diterpenes, Kaurane/*pharmacology
MH  - Drug Synergism
MH  - Endoplasmic Reticulum Stress/drug effects
MH  - ErbB Receptors/genetics
MH  - Humans
MH  - Laryngeal Neoplasms/*drug therapy
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/drug effects/physiology
MH  - RNA, Small Interfering/genetics
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Cetuximab
OT  - ER stress
OT  - Laryngeal squamous cell carcinoma cells
OT  - Mitochondrial pathway
OT  - Oridonin
OT  - Synergistic apoptosis
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/05/15 06:00
MHDA- 2021/03/13 06:00
CRDT- 2020/05/15 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/05/08 00:00 [revised]
PHST- 2020/05/09 00:00 [accepted]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/03/13 06:00 [medline]
PHST- 2020/05/15 06:00 [entrez]
AID - S0887-2333(20)30070-9 [pii]
AID - 10.1016/j.tiv.2020.104885 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2020 Sep;67:104885. doi: 10.1016/j.tiv.2020.104885. Epub 2020 
      May 12.