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.
Highlights
Cucurbitacins are tetracyclic triterpenes isolated from plant in the Cucurbitaceae families that has been used in traditional medicine for centuries [1,2]
Each group of cells were incubated with specified concentrations of cucurbitacin B, ranging from 1 to 100 mg/ml and the cells were assessed for their viability using MTS assay at 48 h post incubation
Cumulative evidences from previous reports showed that cucurbitacin B has anticancer activity in human cancer cells [38,39]
Summary
Cucurbitacins are tetracyclic triterpenes isolated from plant in the Cucurbitaceae families that has been used in traditional medicine for centuries [1,2]. Cucurbitacins have potential to be used as a favorable phytochemical for cancer prevention [3] and the compounds continue to be structural improvement for the future chemotherapeutic approach. Previous studies showed that some of these compounds have a broad range of biological effects, including anti-inflammatory, hepatoprotective and anticancer activities [4,5,6,7,8,9,10]. Several types of cucurbitacin compounds have been studied in vitro and in vivo for their anticancer effects. Cucurbitacin E treatment can inhibit the viability of pancreatic cancer cells (PANC-1) and induce apoptosis via suppression of STAT3 phosphorylation and up-regulation of p53 [8]. Cucurbitacin E inhibits the proliferation of prostate cancer cells and causes disruption of the cytoskeleton structure of actin and vimentin [11]. Cucurbitacin I was shown to inhibit nasopharyngeal carcinoma cell (NPC)
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