Genistein induces apoptosis by the inactivation of the IGF-1R/p-Akt signaling pathway in MCF-7 human breast cancer cells

Cucurbitacins are triterpenoids commonly found in Cucurbitaceae and Cruciferae and have long been used in traditional medicine. Cucurbitacins demonstrate anti-inflammatory and anti-cancer activities. We investigated whether cucurbitacin D affects viability in breast cancer cells and its mechanism of action. An MTT assay was used to measure the viability of breast cancer cells. Western blot analysis was used to measure the expression of various modulators, such as p-p53, p-Stat3, p-Akt, and p-NF-κB. Doxorubicin and cucurbitacin D affected the viability of MCF7, MDA-MB-231, and SKBR3 cells. Cucurbitacin D and doxorubicin increased p-p53 expression in MCF7, SKBR3, and MDA-MB-231 cells. Cucurbitacin D suppressed p-Akt, p-NF-κB, and p-Stat3 expression in MCF7, MDA-MB-231, and SKBR3 cells. Doxorubicin alone did not decrease p-Akt and p-Stat3 levels. Cucurbitacin D decreased p-NF-κB and p-Stat3 levels. Doxorubicin in combination with cucurbitacin D increased p-p53 levels and suppressed Akt, NF-κB, Stat3, and Bcl-2 expression more than cucurbitacin D alone. Our results clearly demonstrate that cucurbitacin D could be a useful compound for treating human breast cancer.

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Anthocyanins Isolated from Vitis coignetiae Pulliat Enhances Cisplatin Sensitivity in MCF-7 Human Breast Cancer Cells through Inhibition of Akt and NF-κB Activation

Molecules ◽

10.3390/molecules25163623 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3623 ◽

Cited By ~ 1

Author(s):

Anjugam Paramanantham ◽

Min Jeong Kim ◽

Eun Joo Jung ◽

Hye Jung Kim ◽

Seong-Hwan Chang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Cell Phenotype ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Anti Cancer ◽

Mcf 7

Anthocyanins isolated from Vitis coignetiae Pulliat (Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-κB which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-κB and p-IκB and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-κB and p-IκB in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-α treatment, AIMs augmented CDDP efficacy with inhibition of NF-κB activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-κB activity of MCF-7 cells that show relative intrinsic CDDP resistance.

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