PMID- 38521250
OWN - NLM
STAT- MEDLINE
DCOM- 20240416
LR  - 20240503
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 97
DP  - 2024 May
TI  - DMC triggers MDA-MB-231 cells apoptosis via inhibiting protective autophagy and 
      PI3K/AKT/mTOR pathway by enhancing ROS level.
PG  - 105809
LID - S0887-2333(24)00039-0 [pii]
LID - 10.1016/j.tiv.2024.105809 [doi]
AB  - DMC, a kind of compound derived from the dry flower buds of Cleistocalyx 
      operculatus, has been shown to inhibit the growth of various cancer cells, but 
      research on triple-negative breast cancer cells remains scarce. To explore this 
      issue, MDA-MB-231 cells were selected, and the results showed that DMC has strong 
      proliferation inhibit effects on this kind of cells. The inhibit rate of 30 muM 
      DMC incubated for 24 h was 56.25%, and 40.6% cells were arrested under the G2/M 
      phase. The levels of pro-apoptosis protein Bax and active caspase-3, cleaved PARP 
      and cell cycle related proteins, such as p21 and p27 increased, but apoptosis 
      regulators, like Bcl-2, Cdc 2, Cyclin B1, and LC3 II decreased dramatically. In 
      addition, DMC induced the accumulation of autophagosomes and autophagic 
      substrates, and the combination of DMC with CQ promoted apoptosis of MDA-MB-231 
      cells, which suggested that DMC induced apoptosis partly by blocking autophagy 
      flow. Moreover, the phosphorylation levels of phosphatidylinositol 3-kinase 
      (PI3K), protein kinase B (AKT), and its mechanistic target of rapamycin kinase 
      (mTOR) were also decreased after 30 muM DMC incubating for 24 h. The proteins play 
      a critical role in cell proliferation, apoptosis, and autophagy modulation. The 
      inhibition of autophagy flow and PI3K/AKT/mTOR pathway could be reversed after 
      being treated with ROS scavenger NAC. Altogether, the results of the present 
      study suggest that DMC effectively induces apoptosis and growth inhibition in 
      MDA-MB-231 cells through blocking autophagy flow and regulating the PI3K/AKT/mTOR 
      pathway by increasing ROS level.
CI  - Copyright (c) 2024 Elsevier Ltd. All rights reserved.
FAU - Jiang, Yu
AU  - Jiang Y
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China.
FAU - Xu, Sunjie
AU  - Xu S
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China.
FAU - Guo, Miaomiao
AU  - Guo M
AD  - Key Laboratory of Cosmetic, China National Light Industry, Beijing Technology and 
      Business University, No. 11/33, Fucheng Road, Beijing 100048, China.
FAU - Lu, Zhi
AU  - Lu Z
AD  - Technology Center, Shanghai Inoherb Cosmetics Co. Ltd., 121 Chengyin Road, 
      Shanghai 200083, China.
FAU - Wei, Xing
AU  - Wei X
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China.
FAU - An, Faliang
AU  - An F
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China; Marine Biomedical Science and Technology 
      Innovation Platform of Lin-gang Special Area, No.4 Lane 218, Haiji Sixth Road, 
      Shanghai 201306, China. Electronic address: flan2016@ecust.edu.cn.
FAU - Xin, Xiujuan
AU  - Xin X
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China. Electronic address: xinxj@ecust.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240321
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis
MH  - Autophagy
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - MDA-MB-231 Cells
MH  - *Phosphatidylinositol 3-Kinase
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - DMC
OT  - MDA-MB-231 cells
OT  - PI3K-AKT-mTOR pathway
COIS- Declaration of competing interest All authors declare no financial or commercial 
      conflicts of interest with this work, and warrant that the article is the 
      authors' original work, and hasn't received prior publication or under 
      consideration for publication elsewhere.
EDAT- 2024/03/24 00:42
MHDA- 2024/04/16 12:42
CRDT- 2024/03/23 20:39
PHST- 2023/10/07 00:00 [received]
PHST- 2024/03/13 00:00 [revised]
PHST- 2024/03/17 00:00 [accepted]
PHST- 2024/04/16 12:42 [medline]
PHST- 2024/03/24 00:42 [pubmed]
PHST- 2024/03/23 20:39 [entrez]
AID - S0887-2333(24)00039-0 [pii]
AID - 10.1016/j.tiv.2024.105809 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2024 May;97:105809. doi: 10.1016/j.tiv.2024.105809. Epub 2024 
      Mar 21.