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Novel Therapeutic Combination Targets the Growth of Letrozole-Resistant Breast Cancer through Decreased Cyclin B1

Jankiben R Patel1, Bipika Banjara1, Afia Ohemeng1

  • 1Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.

Nutrients
|April 13, 2023
PubMed

Insights

Glyceollin and lapatinib combination therapy shows promise for treating letrozole-resistant breast cancer. This combination selectively induces cell cycle arrest in resistant cells, offering a new therapeutic strategy for hormone-refractory tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Breast cancer cells can develop resistance to letrozole, a common aromatase inhibitor (AI).
  • This resistance is associated with overexpression of EGFR, MAPK, and HER2, leading to increased cell motility and epithelial-to-mesenchymal transition (EMT).
  • Glyceollin has shown potential in inhibiting cancer cell proliferation and tumor progression, particularly in triple-negative breast cancer (TNBC) and estrogen-independent cells.

Purpose of the Study:

  • To investigate the efficacy of combining glyceollin with lapatinib in hormone-independent, letrozole-resistant breast cancer cells (LTLT-Ca).
  • To compare the effects of this combination therapy on resistant cells versus AI-sensitive breast cancer cells (AC-1).
  • To determine if the combination therapy can decrease the expression of proteins involved in proliferation and cell cycle progression.

Main Methods:

  • Treatment of AI-sensitive (AC-1) and AI-resistant (LTLT-Ca) breast cancer cells with glyceollin and lapatinib in combination.
  • Assessment of cell proliferation and migration inhibition.
  • Analysis of cell cycle phase distribution (S and G2/M arrest).
  • Evaluation of cyclin B1 expression levels.

Main Results:

  • Glyceollin and lapatinib combination treatment demonstrated comparable inhibitory effects on proliferation and migration in both LTLT-Ca and AC-1 cells.
  • The combination therapy selectively induced S and G2/M phase cell cycle arrest in LTLT-Ca cells.
  • This selective cell cycle arrest was mediated by a decrease in cyclin B1 expression.

Conclusions:

  • Combination therapy with glyceollin and lapatinib offers a potential strategy to target hormone-refractory breast tumors.
  • The selective induction of cell cycle arrest in letrozole-resistant cells presents a unique therapeutic opportunity.
  • Further research into this combinatorial approach may lead to novel treatments for advanced breast cancer.
Keywords:
aromatase inhibitorsbreast cancercancer stem cellscell cycleendocrine resistanceletrozolemammospheresphytochemicals

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