The Effectiveness of Cucurbitacin B in BRCA1 Defective Breast Cancer Cells

Abstract

Cucurbitacin B (CuB) is one of the potential agents for long term anticancer chemoprevention. Cumulative evidences has shown that cucurbitacin B provides potent cellular biological activities such as hepatoprotective, anti-inflammatory and antimicrobial effects, but the precise mechanism of this agent is not clearly understood. We examine the biological effects on cancer cells of cucurbitacin B extracted from a Thai herb, Trichosanthes cucumerina L. The wild type (wt) BRCA1, mutant BRCA1, BRCA1 knocked-down and BRCA1 overexpressed breast cancer cells were treated with the cucurbitacin B and determined for the inhibitory effects on the cell proliferation, migration, invasion, anchorage-independent growth. The gene expressions in the treated cells were analyzed for p21/Waf1, p27Kip1 and survivin. Our previous study revealed that loss of BRCA1 expression leads to an increase in survivin expression, which is responsible for a reduction in sensitivity to paclitaxel. In this work, we showed that cucurbitacin B obviously inhibited knocked-down and mutant BRCA1 breast cancer cells rather than the wild type BRCA1 breast cancer cells in regards to the cellular proliferation, migration, invasion and anchorage-independent growth. Furthermore, forcing the cells to overexpress wild type BRCA1 significantly reduced effectiveness of cucurbitacin B on growth inhibition of the endogenous mutant BRCA1 cells. Interestingly, cucurbitacin B promotes the expression of p21/Waf1 and p27Kip1 but inhibit the expression of survivin. We suggest that survivin could be an important target of cucurbitacin B in BRCA1 defective breast cancer cells.

Inhibition of HER2-integrin signaling by Cucurbitacin B leads to in vitro and in vivo breast tumor growth suppression

“…This study showed an IC50 of 8μM in MDA-MB-231 cells after 48h of treatment. On the other hand, Promkan et al observed an IC50 of 70μM (38.9μg/ml) after 48h of treatment [44]. In contrast to these studies, our study showed significantly reduced effective concentrations of CuB.…”

Evaluation of phenolic compounds, antioxidant and antimicrobial activities from transgenic hairy root cultures of gherkin ( Cucumis anguria L.)

“…The gherkin is also used for traditional medicinal purpose such as stomach ache, jaundice, hemorrhoids and preventing stone formation in kidney (Jeyakumar et al, 2014). It was previously reported that there are many useful phytochemical constituents from gherkin, for example cucurbitacin B, cucurbitacin D and cucurbitacin G. Cucurbitacin B have potential to be used as a favorable phytochemical for cancer prevention (Promkan et al, 2013). Gherkin plant and vegetable contains of many potential compounds such as phenolics, flavonoids, tannins, alkaloids, saponins and steroids which contained high level of antioxidant activity.…”

Cucurbitacin B inhibits growth and induces apoptosis through the JAK2/STAT3 and MAPK pathways in SH-SY5Y human neuroblastoma cells

“…Cucurbitacin B (CuB) is one of the most abundant forms of cucurbitacins and the most widely used as an anticancer agent. It has significant anti-inflammatory activity and is used traditionally to treat hepatitis (9). Studies indicate that CuB is capable of inhibiting the growth of a wide spectrum of malignant human cells, including myeloid leukemia, breast cancer, glioblastoma multiforme, pancreatic cancer, laryngeal cancer, melanoma and osteosarcoma cells (10)(11)(12)(13)(14)(15)(16).…”