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Manganese Oxide Nanoparticle Synthesis by Thermal Decomposition of Manganese(II) Acetylacetonate
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A novel manganese complex, Mn-(II) N-(2-hydroxy acetophenone) glycinate overcomes multidrug-resistance in cancer

Ruma Dey Ghosh1, Kaushik Banerjee, Satyajit Das

  • 1Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|May 14, 2013
PubMed

Insights

A novel manganese complex, manganese N-(2-hydroxy acetophenone) glycinate (MnNG), shows promise in overcoming multidrug resistance (MDR) in cancer. This compound effectively induced apoptosis in resistant leukemia cells and extended survival in mice with resistant tumors.

Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) significantly hinders effective cancer chemotherapy.
  • Despite advances, many cancers remain incurable due to drug resistance.
  • Novel therapeutic strategies are crucial to overcome chemotherapy resistance.

Purpose of the Study:

  • To synthesize and evaluate a novel manganese (II) chelate, manganese N-(2-hydroxy acetophenone) glycinate (MnNG).
  • To assess the efficacy of MnNG in overcoming drug-resistant cancer models.
  • To investigate the mechanism of action of MnNG in inducing cancer cell death.

Main Methods:

  • Synthesis of manganese N-(2-hydroxy acetophenone) glycinate (MnNG).
  • Antiproliferative activity assessment on doxorubicin-resistant (CEM/ADR 5000) and sensitive (CCRF-CEM) human T lymphoblastic leukemia cells.
  • In vivo studies using Swiss albino mice bearing Ehrlich ascites carcinoma cells (sensitive and resistant sublines).
  • Evaluation of apoptosis induction and reactive oxygen species generation.

Main Results:

  • MnNG demonstrated significant antiproliferative activity against doxorubicin-resistant leukemia cells.
  • MnNG induced apoptosis in CEM/ADR 5000 cells, likely via reactive oxygen species generation.
  • Intraperitoneal administration of MnNG at non-toxic doses significantly increased lifespan in mice bearing both sensitive and resistant Ehrlich ascites carcinoma.

Conclusions:

  • Manganese N-(2-hydroxy acetophenone) glycinate (MnNG) is a promising novel compound for combating multidrug-resistant cancers.
  • MnNG exhibits potent anti-cancer effects through apoptosis induction and in vivo efficacy.
  • Further research into MnNG as a therapeutic agent for resistant cancers is warranted.
Keywords:
2′,7′-dihydrodichlorofluorescin diacetate3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide5,5′- Dithio bis(2-nitrobenzoic acid)ALPApoptosisDTNBEACEhrlich ascites carcinomaFITCGSHH(2)-DCFDAIC(50)LD(50)Leukemic cellsMDRMTTManganese complexMnNGMultidrug resistanceP-glycoproteinP-gpPHAGPIROSRT-PCRSGOTSGPTalkaline phosphatasedose for 50% death of animalsdose for 50% growth inhibition of cellfluoroscein isothiocyanate conjugateglutathionemanganese N-(2-hydroxy acetophenone) glycinatemultidrug resistancepotassium N-(2-hydroxy acetophenone) glycinatepropidium iodidereactive oxygen speciesreverse transcription-polymerase chain reactionserum glutamate ortho-transferaseserum glutamine pyruvate transaminase

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