PMID- 35530150
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 12
IP  - 3
DP  - 2022 Mar
TI  - c-MYC-mediated TRIB3/P62(+) aggresomes accumulation triggers paraptosis upon the 
      combination of everolimus and ginsenoside Rh2.
PG  - 1240-1253
LID - 10.1016/j.apsb.2021.09.014 [doi]
AB  - The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung 
      cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is 
      modest. Here, we identified that ginsenoside Rh2, an active component of Panax 
      ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor 
      everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the 
      hepatic fat accumulation caused by everolimus in xenograft nude mice models. The 
      combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced 
      caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, 
      indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. 
      Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor 
      tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 
      (TRIB3)/P62(+) aggresomes and consequently triggered paraptosis, bypassing the 
      classical c-MYC/MAX pathway. Our study offers a potential effective and safe 
      strategy for the treatment of lung cancer. Moreover, we have identified a new 
      mechanism of TRIB3/P62(+) aggresomes-triggered paraptosis and revealed a unique 
      function of c-MYC.
CI  - (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Su, Min-Xia
AU  - Su MX
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Xu, Yu-Lian
AU  - Xu YL
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Jiang, Xiao-Ming
AU  - Jiang XM
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Huang, Mu-Yang
AU  - Huang MY
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Zhang, Le-Le
AU  - Zhang LL
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Yuan, Luo-Wei
AU  - Yuan LW
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Xu, Xiao-Huang
AU  - Xu XH
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Zhu, Qi
AU  - Zhu Q
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Gao, Jian-Li
AU  - Gao JL
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 
      310000, China.
FAU - Lu, Jia-Hong
AU  - Lu JH
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Chen, Xiuping
AU  - Chen X
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Huang, Ming-Qing
AU  - Huang MQ
AD  - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 
      350000, China.
FAU - Wang, Yitao
AU  - Wang Y
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
FAU - Lu, Jin-Jian
AU  - Lu JJ
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macao 999078, China.
AD  - MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao 
      999078, China.
LA  - eng
PT  - Journal Article
DEP - 20210922
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC9072243
OTO - NOTNLM
OT  - Aggresomes
OT  - Everolimus
OT  - Ginsenoside Rh2
OT  - Lung cancer
OT  - P62
OT  - Paraptosis
OT  - TRIB3
OT  - c-MYC
EDAT- 2022/05/10 06:00
MHDA- 2022/05/10 06:01
PMCR- 2021/09/22
CRDT- 2022/05/09 04:19
PHST- 2021/06/17 00:00 [received]
PHST- 2021/08/30 00:00 [revised]
PHST- 2021/08/31 00:00 [accepted]
PHST- 2022/05/09 04:19 [entrez]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/05/10 06:01 [medline]
PHST- 2021/09/22 00:00 [pmc-release]
AID - S2211-3835(21)00356-7 [pii]
AID - 10.1016/j.apsb.2021.09.014 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2022 Mar;12(3):1240-1253. doi: 10.1016/j.apsb.2021.09.014. Epub 
      2021 Sep 22.