Ncentration of 25 ug/ml (Fig. 9C).DiscussionDiscovery of local medicinal plants provide an important source of the naturally derived new antiMadrasin web cancer drug development including Taxol [36,37]. Cumulative evidences from previous reports showed that cucurbitacin B has anticancer activity in human cancer cells [38,39]. We previously reported that cucurbitacin B inhibits growth and telomerase activity in breast cancer cell lines (T47D, SKBR-3, and MCF-7). This agent exerts an obvious inhibitory effect in the estrogen receptor (ER)-negative SKBR-3 cells. Cucurbitacin B also inhibits hTERT and c-Myc expression, implying that it exerts an anticancer effect by inhibiting telomerase via down regulating both the hTERT and c-Myc expression in breast cancer cells [17]. Other studies showed that different cucurbitacin species could also modify SPDB biological activity biological activities of cancer cells. For instance, cucurbitacin B/E glucosides can induce cell cycle arrest at G2/M as well as induce apoptosis in MCF-7 and MDA-MB-231 human breast cancer cells [14]. Cucurbitacin I and Q were shown to specifically inhibit STAT3 phosphorylation which contributes to the proliferation of cancer cells [12]. In this work, we elaborate the effects of cucurbitacin B on breast cancer cells. The anticancer bioactivities of cucurbitacin B on the four breast cancer cell lines were determined. Among the two cell lines with endogenous expression of wild type BRCA1 (MCF-7 and MDA-MB-231), MCF-7 cells are ER positive whereas MDAMB-231 cells are ER negative. The other two cell lines are endogenous mutant BRCA1 breast cancer cells. MDA-MB-436 possessed 5396+1G.A mutation in the splice donor site of exon 20 and has ER negative whereas HCC1937 has the insertion of a cytosine at position 5382 of BRCA1. This mutated type frequently observed in Ashkenazi Jewish. HCC1937 has also negative for ER, PR and Her2/neu [34]. Invasion and metastasis are the major interest in the study on bioactivity of drug in cancer. These two cancer behaviors result in the failure of therapeutic intervention and death. Some report showed that cucurbitacin I can inhibit migration of keloid fibroblasts [40] and also reduces the invasiveness of nasopharyngeal carcinoma cell lines with elevate STAT3 activation [41]. However, the biological effects of cucurbitacin compounds on migration and invasion of breast cancer cells and their possible mechanism have not been completely understood. The 18325633 reduction of cells invasion and migration could partly due to inhibitory effect of cucurbitacin B on cell viability. The other mechanisms may also involve in the effect of cucurbitacin B on these processes. Recently, Duangmano et al. (2012) [42] reported that cucurbitacin B obviously interferes with the microtubule network, which could be one possible reason for the reduced migration and invasion upon cucurbitacin B treatment. We compared the effects of cucurbitacin B in BRCA1 knocked-down cells with the wild type BRCA1 harboring cells. The results indicated that cucurbitacin B inhibits cellular proliferation, migration, invasion and ability of anchorageindependent growth of the BRCA1 knocked-down breast cancer cells while this compound exerts a minimal effect on the wild type BRCA1 breast cancer cells. Results from BRCA1 mutant cells areFunctional BRCA1 abrogates cytotoxic sensitivity to cucurbitacin B of endogenous defective BRCA1 breast cancer cellsAs shown in Figure 6, endogenous BRCA1 defective cancer cells (MDA-MB-436, HCC1937) exhibit.Ncentration of 25 ug/ml (Fig. 9C).DiscussionDiscovery of local medicinal plants provide an important source of the naturally derived new anticancer drug development including Taxol [36,37]. Cumulative evidences from previous reports showed that cucurbitacin B has anticancer activity in human cancer cells [38,39]. We previously reported that cucurbitacin B inhibits growth and telomerase activity in breast cancer cell lines (T47D, SKBR-3, and MCF-7). This agent exerts an obvious inhibitory effect in the estrogen receptor (ER)-negative SKBR-3 cells. Cucurbitacin B also inhibits hTERT and c-Myc expression, implying that it exerts an anticancer effect by inhibiting telomerase via down regulating both the hTERT and c-Myc expression in breast cancer cells [17]. Other studies showed that different cucurbitacin species could also modify biological activities of cancer cells. For instance, cucurbitacin B/E glucosides can induce cell cycle arrest at G2/M as well as induce apoptosis in MCF-7 and MDA-MB-231 human breast cancer cells [14]. Cucurbitacin I and Q were shown to specifically inhibit STAT3 phosphorylation which contributes to the proliferation of cancer cells [12]. In this work, we elaborate the effects of cucurbitacin B on breast cancer cells. The anticancer bioactivities of cucurbitacin B on the four breast cancer cell lines were determined. Among the two cell lines with endogenous expression of wild type BRCA1 (MCF-7 and MDA-MB-231), MCF-7 cells are ER positive whereas MDAMB-231 cells are ER negative. The other two cell lines are endogenous mutant BRCA1 breast cancer cells. MDA-MB-436 possessed 5396+1G.A mutation in the splice donor site of exon 20 and has ER negative whereas HCC1937 has the insertion of a cytosine at position 5382 of BRCA1. This mutated type frequently observed in Ashkenazi Jewish. HCC1937 has also negative for ER, PR and Her2/neu [34]. Invasion and metastasis are the major interest in the study on bioactivity of drug in cancer. These two cancer behaviors result in the failure of therapeutic intervention and death. Some report showed that cucurbitacin I can inhibit migration of keloid fibroblasts [40] and also reduces the invasiveness of nasopharyngeal carcinoma cell lines with elevate STAT3 activation [41]. However, the biological effects of cucurbitacin compounds on migration and invasion of breast cancer cells and their possible mechanism have not been completely understood. The 18325633 reduction of cells invasion and migration could partly due to inhibitory effect of cucurbitacin B on cell viability. The other mechanisms may also involve in the effect of cucurbitacin B on these processes. Recently, Duangmano et al. (2012) [42] reported that cucurbitacin B obviously interferes with the microtubule network, which could be one possible reason for the reduced migration and invasion upon cucurbitacin B treatment. We compared the effects of cucurbitacin B in BRCA1 knocked-down cells with the wild type BRCA1 harboring cells. The results indicated that cucurbitacin B inhibits cellular proliferation, migration, invasion and ability of anchorageindependent growth of the BRCA1 knocked-down breast cancer cells while this compound exerts a minimal effect on the wild type BRCA1 breast cancer cells. Results from BRCA1 mutant cells areFunctional BRCA1 abrogates cytotoxic sensitivity to cucurbitacin B of endogenous defective BRCA1 breast cancer cellsAs shown in Figure 6, endogenous BRCA1 defective cancer cells (MDA-MB-436, HCC1937) exhibit.
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