Dendrosomal Nano-Curcumin Modulates P-Glycoprotein Activity and Induces Apoptosis in Wild Type and P53-Mutant Breast Cancer Cell Lines

Abstract

Background: Dendrosomal nano-curcumin (DNC) represents an enormous potential to serve as a therapeutic anticancer agent. Here, we investigated the effect of DNC on wild type- and p53-mutant breast cancer cells. Methods: MCF-7 and T47D cells were treated with DNC and investigated for cell viability through MTT assay. The mode of death was analyzed using Annexin V/FITC staining and PARP cleavage assays. Flow cytometric efflux and cell swelling tests were employed to assess the p-glycoprotein (P-gp) transporter activity. Moreover, real-time PCR was employed to study the expression of Bax, Bcl-2 as well as survivin and its ΔEx3 splicing variant. Results: Our findings confirmed that DNC repressed cancer cell proliferation by induction of apoptosis. Additionally, DNC significantly modulated P-gp function that might lead to improved cellular permanence of curcumin. Malfunction of P-gp activity by DNC demonstrates its capability in reducing the drug resistance of p53-mutant cancer cells. Conclusions: In conclusion, our findings demonstrated that dendrosomal nano-curcumin could be considered an anti-tumor therapeutic for p53-mutant tumor malignancies.

MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets

“…Furthermore, curcumin was found to suppress the proliferation and induce apoptosis of cancer cells ( Ghaderi et al, 2021 ), ( Sobhkhizi et al, 2020 ) as well as impinge MCF-7 cells by upregulating miR-15a and miR-16, which caused downregulation of Bcl-2 ( Fix et al, 2010 ). Curcumin also upregulated miR-34a and miR-181b in breast cancer cell lines and inhibited invasion and metastasis of them ( Guo et al, 2013 ), ( Kronski et al, 2014 ), ( Norouzi et al, 2018 ).…”

Recent findings on the role of wild-type and mutant p53 in cancer development and therapy

“…Also, methods such as chemotherapy, radiotherapy, and immunotherapy with specific targeting of the mutant p53 to suppress tumor growth are becoming a promising approach in the treatment of cancer ( Beckta et al, 2014 ; Huang, 2021 ). Some plant substances and compounds are effective on wild-type and mutant p53 by inducing apoptosis or preventing cell proliferation, for example, Gemini curcumin and dendrosomal nano-curcumin in colorectal and breast cancer cell lines ( Sobhkhizi et al, 2020 ; Ebrahimi et al, 2021 ).…”