PMID- 37038711
OWN - NLM
STAT- MEDLINE
DCOM- 20230714
LR  - 20230718
IS  - 1875-5992 (Electronic)
IS  - 1871-5206 (Linking)
VI  - 23
IP  - 12
DP  - 2023
TI  - 3-Bromopyruvate Inhibits the Growth and Glucose Metabolism of TNBC Xenografts in 
      Nude Mice by Targeting c-Myc.
PG  - 1421-1428
LID - 10.2174/1871520623666230406111833 [doi]
AB  - BACKGROUND: Due to the lack of effective drug treatment, triple-negative breast 
      cancer (TNBC) is prone to recurrence and metastasis after an operation. As a 
      glycolytic inhibitor, 3-bromopyruvic acid (3-BrPA) can inhibit the proliferation 
      and induce apoptosis of TNBC cells. However, whether it has similar effects in 
      animal models remains unclear. OBJECTIVE: To observe the effect of 3-BrPA on the 
      growth and glucose metabolism of human TNBC transplanted tumors in nude mice and 
      to investigate the mechanism. METHODS: We constructed subcutaneous xenografts of 
      human TNBC in nude mice and treated them with low, medium and high concentrations 
      of 3-BrPA. After 15 days, nude mice were sacrificed to detect hexokinase (HK) 
      activity and adenosine triphosphate (ATP) content in tumor tissues. 
      Hematoxylin-eosin (HE) staining was used to detect the damage of transplanted 
      tumors and liver and kidney in nude mice, which 3-BrPA caused. The expression of 
      c-Myc in tumor tissues was detected by Immunohistochemistry (IHC). Terminal 
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was 
      used to detect the apoptosis of tumor tissues. Besides, the expressions of Cytc, 
      Bax, Bcl-2 and Caspase-9 were detected by Western blotting. RESULTS: Compared 
      with the control group, intraperitoneal injection of 3-BrPA inhibited the growth 
      of human TNBC transplant tumors, decreased HK activity and ATP production in 
      tumor tissues, disrupted the tissue structure of transplant tumors, and did not 
      significantly damage liver and kidney tissues. IHC staining and Western blotting 
      showed that 3-BrPA could decrease the expression of c-Myc and Bcl-2, increase the 
      expression of Cyt -c, Bax and Caspase-9 expression and promote apoptosis in tumor 
      tissues. CONCLUSION: The above data indicate that 3-BrPA inhibits the growth of 
      human TNBC transplanted tumors and promotes their apoptosis. Its anti-cancer 
      mechanism might reduce HK activity by down-regulating c-Myc expression, 
      eventually leading to decreased glycolytic pathway energy production and 
      promoting apoptosis of transplanted tumors.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Pan, Jian-Min
AU  - Pan JM
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
FAU - Li, Jia-Chen
AU  - Li JC
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
FAU - Yang, Cheng
AU  - Yang C
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
FAU - Xiao, Wang-Fa
AU  - Xiao WF
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
FAU - Li, Qi-Shang
AU  - Li QS
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
FAU - Luo, Xiao-Hui
AU  - Luo XH
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
FAU - Zhang, Xiao-Dong
AU  - Zhang XD
AD  - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital 
      of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 530021, P.R. 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Anticancer Agents Med Chem
JT  - Anti-cancer agents in medicinal chemistry
JID - 101265649
RN  - 63JMV04GRK (bromopyruvate)
RN  - EC 3.4.22.- (Caspase 9)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - Mice, Nude
MH  - *Triple Negative Breast Neoplasms/drug therapy
MH  - Caspase 9/metabolism
MH  - Heterografts
MH  - bcl-2-Associated X Protein/metabolism
MH  - Cell Line, Tumor
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Adenosine Triphosphate/pharmacology
MH  - Glucose
OTO - NOTNLM
OT  - 3-bromopyruvic acid
OT  - apoptosis
OT  - c-Myc
OT  - glycolysis
OT  - nude mice
OT  - triple-negative breast cancer
EDAT- 2023/04/12 06:00
MHDA- 2023/07/14 13:06
CRDT- 2023/04/11 02:24
PHST- 2022/09/15 00:00 [received]
PHST- 2023/02/16 00:00 [revised]
PHST- 2023/02/27 00:00 [accepted]
PHST- 2023/07/14 13:06 [medline]
PHST- 2023/04/12 06:00 [pubmed]
PHST- 2023/04/11 02:24 [entrez]
AID - ACAMC-EPUB-130747 [pii]
AID - 10.2174/1871520623666230406111833 [doi]
PST - ppublish
SO  - Anticancer Agents Med Chem. 2023;23(12):1421-1428. doi: 
      10.2174/1871520623666230406111833.