4.6 Article

Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple-Negative Breast Cancer Cell Lines

Journal

PHARMACEUTICALS
Volume 15, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/ph15091075

Keywords

anticancer effect; breast cancer; calcitriol; combined therapy; talazoparib; TNBC; triple-negative breast cancer

Funding

  1. Malaysian Ministry of Higher Education under the grant Fundamental Research Grant Scheme [FRGS/1/2016/SKK02/UCSI/02/1]
  2. Research Excellence & Innovation Grant from UCSI University's Centre of Excellence for Research, Value Innovation and Entrepreneurship [REIG FMS 2020/044]

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This study investigated the effect of combined treatment with calcitriol and talazoparib on triple-negative breast cancer cell lines. The combination significantly inhibited cell proliferation and migration, induced apoptosis and necrosis. This combination could be a promising treatment option for triple-negative breast cancer.
Monotherapy for triple-negative breast cancer (TNBC) is often ineffective. This study aimed to investigate the effect of calcitriol and talazoparib combination on cell proliferation, migration, apoptosis and cell cycle in TNBC cell lines. Monotherapies and their combination were studied for (i.) antiproliferative effect (using real-time cell analyzer assay), (ii.) cell migration (CIM-Plate assay), and (iii.) apoptosis and cell cycle analysis (flow cytometry) in MDA -MB-468 and BT-20 cell lines. The optimal antiproliferative concentration of talazoparib and calcitriol in BT-20 was 91.6 and 10 mu M, respectively, and in MDA-MB-468, it was 1 mM and 10 mu M. Combined treatment significantly increased inhibition of cell migration in both cell lines. The combined treatment in BT-20 significantly increased late apoptosis (89.05 vs. control 0.63%) and S and G2/M populations (31.95 and 24.29% vs. control (18.62 and 12.09%)). Combined treatment in MDA-MB-468 significantly increased the S population (45.72%) and decreased G0/G1 (45.86%) vs. the control (26.79 and 59.78%, respectively). In MDA -MB-468, combined treatment significantly increased necrosis, early and late apoptosis (7.13, 33.53 and 47.1% vs. control (1.5, 3.1 and 2.83%, respectively)). Talazoparib and calcitriol combination significantly affected cell proliferation and migration, induction of apoptosis and necrosis in TNBC cell lines. This combination could be useful as a formulation to treat TNBC.

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