Background
Sodium oxamate as PDK1 and LDHA inhibitor with IC50 values (μg/mL) of 15.60[1]. Sodium oxamate can specifically inhibit LDH-A. Sodium oxamate by down-regulating CDK1/cyclin B1 Pathway induces G2/M cell cycle arrest and promotes apoptotic targets by increasing ROS production in mitochondria[4,5].
Sodium oxamate enhances the suppressive effects of PARP inhibitors on ovarian cancer without BRCA mutations, remarkably promoting the inhibitory effects of PARP inhibitors on wild-type BRCA ovarian cancer cells[3]. In the human PC cell line, Sodium oxamate caused cell inhibition, resulting in increased sensitivity of CRPC cells to DOC, and the combination of DOC and Sodium oxamate promoted apoptosis compared with DOC or Sodium oxamate alone[2].
Sodium oxamate reduces the growth of colorectal cancer in CRC mice, by restoring the down-regulated MMR functional proteins and attenuating chemotherapy resistance to oxaliplatin caused by C. tropicalis[6]. NETosis and lactate accumulation during LPS induced sepsis in mice was inhibited by sodium oxamate [7].
参考文献:
[1]: Kamal S, Derbala HA, et,al. Synthesis, Biological, and Molecular Docking Studies on 4,5,6,7-Tetrahydrobenzo[b]thiophene Derivatives and Their Nanoparticles Targeting Colorectal Cancer. ACS Omega. 2021 Oct 25;6(43):28992-29008. doi: 10.1021/acsomega.1c04063. PMID: 34746589; PMCID: PMC8567357.
[2]: Muramatsu H, Sumitomo M, et,al. Targeting lactate dehydrogenase?A promotes docetaxel?induced cytotoxicity predominantly in castration?resistant prostate cancer cells. Oncol Rep. 2019 Jul;42(1):224-230. doi: 10.3892/or.2019.7171. Epub 2019 May 24. PMID: 31180564.
[3]: Xiang J, Zhou L, et,al. LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells. Aging (Albany NY). 2021 Dec 16;13(24):25920-25930. doi: 10.18632/aging.203780. Epub 2021 Dec 16. PMID: 34919531; PMCID: PMC8751605.
[4]: Thornburg JM, Nelson KK, et,al. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res. 2008;10(5):R84. doi: 10.1186/bcr2154. Epub 2008 Oct 15. PMID: 18922152; PMCID: PMC2614520.
[5]: Zhai X, Yang Y, et,al. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep. 2013 Dec;30(6):2983-91. doi: 10.3892/or.2013.2735. Epub 2013 Sep 19. PMID: 24064966.
[6]: Qu J, Sun Z, et,al. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int J Biol Sci. 2021 Jul 2;17(11):2756-2769. doi: 10.7150/ijbs.59262. PMID: 34345205; PMCID: PMC8326116.
[7]: Awasthi D, Nagarkoti S, et,al. Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis. Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165542. doi: 10.1016/j.bbadis.2019.165542. Epub 2019 Aug 29. PMID: 31473341.
草酸钠作为 PDK1 和 LDHA 抑制剂，IC50 值 (μg/mL) 为 15.60[1]。草酸钠可以特异性抑制LDH-A。草酸钠通过下调 CDK1/cyclin B1 通路诱导 G2/M 细胞周期停滞，并通过增加线粒体中 ROS 的产生促进凋亡靶点[4,5]。
草酸钠增强PARP抑制剂对无BRCA突变卵巢癌的抑制作用，显着促进PARP抑制剂对野生型BRCA卵巢癌细胞的抑制作用[3]。在人 PC 细胞系中，草酸钠引起细胞抑制，导致 CRPC 细胞对 DOC 的敏感性增加，与单独使用 DOC 或草酸钠相比，DOC 和草酸钠联合促进细胞凋亡[2] .
草酸钠通过恢复下调的 MMR 功能蛋白和减弱由热带念珠菌引起的对奥沙利铂的化疗耐药性来减少 CRC 小鼠结直肠癌的生长[6]。草胺酸钠可抑制 LPS 诱导小鼠脓毒症期间的 NETosis 和乳酸积累[7]。
Protocol
| Cell experiment [1]: |
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Cell lines
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BRCA ovarian cancer cells:A2780 and SKOV3
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Preparation Method
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Cell proliferation is evaluated using a Cell Counting Kit-8. SKOV3 cells and A2780 cells are seeded in a 96-well culture plates at a density of 2 105 cells/well and incubated with different concentrations of the drugs for different times(Sodium oxamate).
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Reaction Conditions
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50 mM Sodium oxamate for 24 h
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Applications
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Sodium oxamate enhances the suppressive effects of PARP inhibitors on ovarian cancer without BRCA mutations, remarkably promoting the inhibitory effects of PARP inhibitors on wild-type BRCA ovarian cancer cells.
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| Animal experiment [2]: |
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Animal models
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Four-week-old male BALB/c nude mice of CRC xenograft
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Preparation Method
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C. tropicalis was given by multipoint intratumoral injection, twice per week for three weeks.Oxaliplatin (10 mg/kg) and Sodium oxamate (500 mg/kg) were administered by intraperitoneal injection, twice per week for three weeks. The length and width of the tumors were measured every three days.
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Dosage form
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500 mg/kg Sodium oxamate Twice a week for three weeks
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Applications
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Sodium oxamate reduces the growth of colorectal cancer in CRC mice, by restoring the down-regulated MMR functional proteins and attenuating chemotherapy resistance to oxaliplatin caused by C. tropicalis.
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参考文献:
[1]. Xiang J, Zhou L, He Y, Wu S. LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells. Aging (Albany NY). 2021 Dec 16;13(24):25920-25930. doi: 10.18632/aging.203780. Epub 2021 Dec 16. PMID: 34919531; PMCID: PMC8751605.
[2]. Qu J, Sun Z, Peng C, Li D, Yan W, Xu Z, Hou Y, Shen S, Chen P, Wang T. C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int J Biol Sci. 2021 Jul 2;17(11):2756-2769. doi: 10.7150/ijbs.59262. PMID: 34345205; PMCID: PMC8326116.
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