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Published on: February 16, 2015

Arsenic trioxide overcomes apoptosis inhibition in K562/ADM cells by regulating vital components in apoptotic pathway

Dong-Hai Wang1, Hu-Lai Wei, Huai-Shun Zhao

  • 1Molecular Cell Biology Research Center, Key Laboratory of Preclinical Study for Drugs of Gansu Province, Lanzhou University School of Medicine, Lanzhou 730000, PR China.

Pharmacological Research
|June 28, 2005
PubMed

Insights

Arsenic trioxide (As(2)O(3)) induces apoptosis and reverses chemotherapy resistance in multidrug-resistant leukemia cells. It modulates key factors like FAS, P53, and P-glycoprotein, offering a potential strategy against resistant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Arsenicals demonstrate anti-tumor effects in various cancers, including leukemia.
  • The efficacy of arsenicals against chemotherapy-resistant leukemia remains poorly understood, posing a significant clinical challenge.

Purpose of the Study:

  • To investigate the effects of arsenic trioxide (As(2)O(3)) on apoptosis induction in multidrug-resistant K562/ADM leukemic cells.
  • To elucidate the underlying mechanisms of As(2)O(3)-induced apoptosis and reversal of drug resistance.

Main Methods:

  • Microscopy, flow cytometry (FCM), and DNA electrophoresis were used to assess apoptosis and cell cycle arrest.
  • FCM was employed to analyze protein expression levels of FAS, P53, P-glycoprotein (P-gp), and BCL-2.
  • Reverse transcription polymerase chain reaction (RT-PCR) was utilized to quantify mRNA levels of FAS, caspase-3, and MDR1.
  • Caspase-3 activity assays were performed.

Main Results:

  • As(2)O(3) treatment resulted in G2/M phase arrest and apoptosis in K562/ADM cells.
  • Increased levels of FAS and P53 proteins and decreased P-glycoprotein (P-gp) were observed.
  • mRNA levels of FAS and caspase-3 were upregulated, while MDR1 mRNA was downregulated.
  • Caspase-3 activity was enhanced, whereas BCL-2 protein expression remained unaffected.

Conclusions:

  • As(2)O(3) effectively induces apoptosis and overcomes drug resistance in K562/ADM cells.
  • The mechanism involves modulation of key apoptotic factors, including FAS, P53, and P-glycoprotein.
  • As(2)O(3) presents a promising therapeutic agent for overcoming chemotherapy resistance in leukemia.

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