PMID- 35813464
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20220812
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 18
IP  - 9
DP  - 2022
TI  - Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through 
      ROS-mediated inhibition of PI3K/AKT signaling pathway.
PG  - 3714-3730
LID - 10.7150/ijbs.69989 [doi]
AB  - Novel drugs are required for non-small cell lung cancer (NSCLC) treatment 
      urgently. Repurposing old drugs as new treatments is a practicable approach with 
      time and cost savings. Some studies have shown that carrimycin, a Chinese Food 
      and Drug Administration (CFDA)-approved macrolide antibiotic, possesses potent 
      anti-tumor effects against oral squamous cell carcinoma. However, its detailed 
      component and underlying mechanisms in anti-NSCLC remain unknown. In our study, 
      isovalerylspiramycin I (ISP-I) was isolated from carrimycin and demonstrated a 
      remarkable anti-NSCLC efficacy in vitro and in vivo with a favorable safety 
      profile. It has been proven that in NSCLC cell lines H460 and A549, ISP-I could 
      induce G2/M arrest and apoptosis, which was mainly attributed to ROS accumulation 
      and subsequently PI3K/AKT signaling pathway inhibition. Numerous downstream genes 
      including mTOR and FOXOs were also changed correspondingly. An observation of 
      NAC-induced reverse effect on ISP-I-leading cell death and PI3K/AKT pathway 
      inhibition, emphasized the necessity of ROS signaling in this event. Moreover, we 
      identified ROS accumulation and PI3K/AKT pathway inhibition in tumor xenograft 
      models in vivo as well. Taken together, our study firstly reveals that ISP-I is a 
      novel ROS inducer and may act as a promising candidate with multi-target and low 
      biological toxicity for anti-NSCLC treatment.
CI  - (c) The author(s).
FAU - Liu, Zeyu
AU  - Liu Z
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
FAU - Huang, Moli
AU  - Huang M
AD  - Department of Bioinformatics, School of Biological and Basic Medical Sciences, 
      Soochow University, Suzhou, 215123, China.
FAU - Hong, Yue
AU  - Hong Y
AD  - Stem Cell Center, Shanghai Jiao Tong University Affiliated Sixth People's 
      Hospital, Shanghai, 200233, China.
FAU - Wang, Shaoyang
AU  - Wang S
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
FAU - Xu, Yongle
AU  - Xu Y
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
FAU - Zhong, Cheng
AU  - Zhong C
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
FAU - Zhang, Jingyuan
AU  - Zhang J
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
FAU - Zhuang, Zhengping
AU  - Zhuang Z
AD  - Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, MD 20892, USA.
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Shan, Shan
AU  - Shan S
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
FAU - Ren, Tao
AU  - Ren T
AD  - Department of Respiratory and Clinical Care Medicine, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong 
      University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220521
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Apoptosis
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - *Carcinoma, Squamous Cell
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - G2 Phase Cell Cycle Checkpoints
MH  - Humans
MH  - *Lung Neoplasms/genetics
MH  - *Mouth Neoplasms
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
PMC - PMC9254468
OTO - NOTNLM
OT  - G2/M arrest
OT  - Isovalerylspiramycin I (ISP-I)
OT  - Non-small cell lung cancer (NSCLC)
OT  - PI3K/AKT signaling pathway
OT  - ROS
OT  - apoptosis
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/07/12 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/01/01
CRDT- 2022/07/11 04:02
PHST- 2021/12/12 00:00 [received]
PHST- 2022/05/10 00:00 [accepted]
PHST- 2022/07/11 04:02 [entrez]
PHST- 2022/07/12 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - ijbsv18p3714 [pii]
AID - 10.7150/ijbs.69989 [doi]
PST - epublish
SO  - Int J Biol Sci. 2022 May 21;18(9):3714-3730. doi: 10.7150/ijbs.69989. eCollection 
      2022.