Telomerase as a Possible Candidate Targeting Therapy in Different Breast Cancer Cell Lines

Salma Aboelela1, Abeer Ashmawy2, Sabry Shaarawy2

  • 1Electron Microscopy Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo Egypt.

Abstract

Insights

Telomerase inhibition using siRNA combined with doxorubicin effectively reduces breast cancer cell viability and induces apoptosis. This combination therapy shows a potentiated cytotoxic effect, offering a promising strategy for breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Telomerase is upregulated in most breast cancers, making it a potential therapeutic target.
  • Targeting telomerase may offer a novel approach to breast cancer treatment.

Purpose of the Study:

  • To investigate the effects of telomerase inhibition by siRNA on breast cancer cell lines.
  • To evaluate the combined effect of doxorubicin and siRNA treatment on breast cancer cells.
  • To determine if the combination potentiates a faster cellular response to chemotherapy.

Main Methods:

  • Utilized Luminal A (MCF-7), triple-negative (MDA-MB-468), and HER-2/neu (SKBR-3) human breast cancer cell lines.
  • Inhibited telomerase using hTERT siRNA and treated with doxorubicin.
  • Assessed telomerase activity (TRAP assay), cell viability (MTT assay), and apoptosis (SEM, Caspase-3/-8 ELISA).

Main Results:

  • hTERT siRNA reduced telomerase activity (>90%) and cell viability (>60%) in most cell lines within 72 hours.
  • The combination of hTERT siRNA and doxorubicin demonstrated a cumulative effect compared to monotherapy (P < 0.05).
  • Scanning electron microscopy confirmed apoptotic morphological changes in treated cells.

Conclusions:

  • Telomerase inhibition is a promising strategy for effective breast cancer treatment.
  • Combining telomerase inhibition with doxorubicin potentiates the drug's cytotoxic effect on breast cancer cells.
  • This combination approach may enhance chemotherapy efficacy in breast cancer.

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