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Published on: November 18, 2014

Effects of BCL-2 suppression by antisense oligonucleotides on additional regulators of apoptosis compensatory change

Marvin Rubenstein1, Courtney M P Hollowell, Patrick Guinan

  • 1Chairman, Division of Cellular Biology, Hektoen Institute for Medical Research, 2240 West Ogden Avenue, Chicago, IL 60612, USA. DrMarv@Prodigy.net

In Vivo (Athens, Greece)
|July 15, 2011
PubMed

Insights

Bispecific antisense oligonucleotides targeting BCL-2 and EGFR show comparable prostate cancer cell growth inhibition to monospecific oligos. This suggests bispecific oligos are effective and may not require caspase-3 activity maintenance for clinical use.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Antisense oligonucleotides (oligos) are investigated for prostate cancer therapy.
  • Bispecific oligos targeting two mRNAs are a novel development.
  • Non-specific effects of oligos can lead to compensatory tumor growth.

Purpose of the Study:

  • To evaluate specific and non-specific effects of mono- and bispecific oligos against BCL-2 on LNCaP cell growth.
  • To assess compensatory apoptosis regulation in response to BCL-2 suppression.

Main Methods:

  • LNCaP cells were treated with monospecific and bispecific antisense oligos targeting BCL-2 and EGFR.
  • Cell growth inhibition was measured.
  • RT-PCR was used to quantify mRNA levels of BCL-2, BAX, caspase-3, and clusterin.

Main Results:

  • Both mono- and bispecific oligos targeting BCL-2 achieved significant, comparable growth inhibition.
  • mRNA suppression of BCL-2 approached 100% for all oligo types.
  • BCL-2 suppression did not affect BAX, but suppressed caspase-3 expression, suggesting a compensatory mechanism.

Conclusions:

  • Bispecific antisense oligos targeting EGFR and BCL-2 are as effective as monospecific oligos for inhibiting prostate cancer cell growth.
  • Compensatory apoptosis regulation may be limited, potentially involving caspase-3.
  • Clinical use of BCL-2-targeting oligos might necessitate maintaining caspase-3 activity.

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