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image of Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer

Abstract

Background

Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin-E was carried out by (NRRL 2178). Moreover, anticancer activity against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated.

Methods

The cucurbitacin-E-glucoside was biotransformed by to cucurbitacin-E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC was calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin-E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined.

Results

The IC value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 µg/ml. LD of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD (24 mg/kg/b.w.) and 1/20 LD (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors.

Conclusions

These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.

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2024-10-09
2024-11-15
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  • Article Type:
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Keywords: Curvularia lunata ; Cucurbitacin-E ; MCF-7 ; DMBA ; P53 ; BRCA1 and BRCA2
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