Viability and cell cycle studies of metastatic triple negative breast cancer cells using low voltage electrical pulses and herbal curcumin

Abstract

Cancer is a disease of cell cycle, characterized by uncontrolled cell division. The tumor suppressor gene p53 plays a major role in cell cycle control, blocking the cell progression at G 1 /S phases. In triple negative breast cancer (TNBC), the lack/mutation of p53 is a common genetic irregularity that promotes survival signals leading to tumorigenesis. Due to its unique molecular profile, aggressive behavior, and metastasis, no targeted therapies exist for TNBC. This motivates our exploration of the influence of Electro-Curcumin-Therapy on the viability, cell cycle and p53 expression profile of TNBC cells. MDA-MB-231, human TNBC cells were treated with curcumin and eight 200 V cm −1 electric pulses (EPs) of either 100 μs or 5 ms duration. The synergy of 5 ms EPs and curcumin reduced viability to as low as 6% at 48 h after treatment. Combining the 100 μs EPs with curcumin arrested 80% cells in the G 0 /G 1 phase. Applying 5 ms EPs with curcumin caused cells to shift from the G 2 phase (9% reduction) to the S phase population (21% increase) compared to control. Combining 100 μs EPs with curcumin significantly downregulated the p53 level, while the p53 level significantly increased for 5 ms EPs with and without curcumin. These results indicate the potent effect of combining EPs and curcumin to effectively cause cell death in TNBC cells with different mechanistic behaviors, while having a much-reduced impact on cell death in normal mammary cells.

Quantitative proteomic analysis of enhanced cellular effects of electrochemotherapy with Cisplatin in triple-negative breast cancer cells

“…Following 4 h treatment, all cells were scraped, washed thrice with ice-cold 1 × PBS with centrifugation at 1,500 rpm at 4 °C, lysed using the RIPA buffer and sonication, as previously 69 . Lysates were cleared of debris with centrifugation at 14000 rpm.…”

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

“…These effects were accompanied by the regulation of Bax, Bcl-2, p16, and p21 expression, which eventually led to apoptosis induction and cell cycle arrest [ 143 ]. In contrast, it has been reported that curcumin treatment decreases the expression level of p53 and phosphorylated p53 (S392, S15, S392) in MDA-MB-231, SKBR3 and EMT6 cells, representing the induction of p53- independent apoptosis in treated cells [ 108 , 144 , 145 , 146 , 147 ]. Moreover, it has been documented that Notch1 overexpression is correlated with a highly expressed mutant p53 (R280K) in MDA-MB-231 cells, in which mutant p53 acts as its transcriptional activator.…”

<p>Resistance and Overcoming Resistance in Breast Cancer</p>

“… 128 Additional studies in BC cell lines showed that ECT increased the cytotoxicity of curcumin treatment by 7-fold, 129 increased apoptosis in MDA-MB-231 cells, and minimally affected the viability of non-cancerous MCF10A cells. 129 , 130 A recent study demonstrated the anticancer effects of ECT against the MDA-MB-231 cell line, which is representative of the TNBC subtype. 131 These effects include the suppression of key proteins involved in the proliferation, differentiation, migration, survival, and apoptosis of cancer cells.…”