Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses

Abstract

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC 50 = 0.19 µM), BT-20 (IC 50 = 0.23 µM) and MDA-MB-468 (IC 50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

Dihydrotanshinone-I modulates Epithelial Mesenchymal Transition (EMT) Thereby Impairing Migration and Clonogenicity of Triple Negative Breast Cancer Cells

“…In this context, the implementation of a complementary treatment might find the solution, as naturally derived compounds offer a great deal of anti-cancer activity. Natural compounds like curcumin, quercetin, berberine, etc have been shown to inhibit TNBC proliferation and aggressiveness (Kundur et al, 2019;El Khalki et al, 2020). In the present manuscript, we investigated the potential of 15,16-dihydrotanshinone-I (DHTS) for its anti-migratory action in TNBC cell lines.…”

Berberine as a Potential Anticancer Agent: A Comprehensive Review

“…Berberine was cytotoxic against all treated TNBC cell lines such as MDA-MB-231, MDA-MB-468, HCC1937, HCC70, HCC38, BT-20, HCC1143, and BT-549. Among all these experimented cell lines, the most sensitive ones were HCC70 (IC 50 = 0.19 µM), BT-20 (IC 50 = 0.23 µM), and MDA-MB-468 (IC 50 = 0.48 µM) [ 45 ]. Using flow cytometry techniques, BBR at 0.5 and 1 µM for 120 and 144 h not only induced cell cycle arrest at first growth (G1) and second-growth (G2)/medium phases, but it also triggered significant apoptosis [ 45 ].…”

Beta-Blockers and Berberine: A Possible Dual Approach to Contrast Neuroblastoma Growth and Progression

“…Meeran et al have showed that BBR treatment-induced apoptosis through the alteration of mitochondrial membrane potential and the cleavage of caspase-3, caspase-9 protein, and PARP in PC-3 prostate cancer cells [ 110 ]. BBR significantly induces apoptosis in MDA-MB-468, HCC70, and BT-20 triple-negative breast cancer cells through the cleavage of caspase-7 and caspase-8 protein in MDA-MB-468 and BT-20 cell line, and by the cleavage of PARP in HCC70 cells [ 111 ]. In addition, Wen et al have reported that the combination of BBR and tamoxifen (TAM) induced cell cycle arrest in the G1 phase and apoptosis through the induction of p21Cip-1 and the increase of the Bax/Bcl-2 ratio in MCF7 and tamoxifen-resistant MCF7/TAMR breast cancer cells [ 112 ].…”