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RISS 인기검색어
- 검색키워드
- 저자 : Bukowska, Barbara (검색결과 3 건)
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Bukowska, Barbara,Rogalska, Aneta,Forma, Ewa,Brys, Magdalena,Marczak, Agnieszka Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3
Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.
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Pawel Pasko,Karolina Bukowska-Strakova,Joanna Gdula-Argasinska,Malgorzata Tyszka-Czochara 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.8
Although rutabaga (Brassica napus L. var. napobrassica) is a popular crop, especially in North Europe and North America, its sprouts are a new kind of vegetable. Rutabaga roots, and particularly sprouts, have not been investigated so far for antioxidant and anticancer effect on human tumor cells (Hep G2). Therefore, in vitro tests were conducted to find out whether rutabaga seeds, roots, and sprouts exert a cytotoxic effect on mammalian cells and combine them with other biological properties of particular parts of the plant. Rutabaga methanol extracts were measured for total phenolic, total flavonoid concentrations, and total antioxidant activity. Cytotoxicity of the investigated extracts was measured using 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay in Chinese hamster ovary cells (CHO-K1) and Hep G2 cells culture. Cell membrane integrity was assessed in CHO-K1 and Hep G2 cells by luminescence ToxiLight BioAssay. The results of the investigation have shown that sprouts have significantly higher antioxidant activity than seeds and roots, which may result from different contents of polyphenols. Rutabaga extracts (especially 8 day sprouts) inhibited the tumor cell line Hep G2 proliferation and had a slight effect on the normal mammalian CHO-K1 culture. An advanced analysis of previously observed morphological changes and cytotoxic properties demonstrated that the evaluated extracts exerted cell death via apoptosis. These findings strongly suggest that one of the biological activities of rutabaga is antiproliferative and proapoptotic potential specific to tumor cells. The obtained results demonstrate the antioxidant property of rutabaga and its potential as a nutritional supplement in cancer prevention. These findings also strongly advocate the application of rutabaga sprouts (especially harvested in conditions presented in this article) in functional food.
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Gajek, Arkadiusz,Denel-Bobrowska, Marta,Rogalska, Aneta,Bukowska, Barbara,Maszewski, Janusz,Marczak, Agnieszka Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18
The purpose of this study was to provide a detailed explanation of the mechanism of bisanthracycline, WP 631 in comparison to doxorubicin (DOX), a first generation anthracycline, currently the most widely used pharmaceutical in clinical oncology. Experiments were performed in SKOV-3 ovarian cancer cells which are otherwise resistant to standard drugs such as cis-platinum and adriamycin. As attention was focused on the ability of WP 631 to induce apoptosis, this was examined using a double staining method with Annexin V and propidium iodide probes, with measurement of the level of intracellular calcium ions and cytosolic cytochrome c. The western blotting technique was performed to confirm PARP cleavage. We also investigated the involvement of caspase activation and DNA degradation (comet assay and immunocytochemical detection of phosphorylated H2AX histones) in the development of apoptotic events. WP 631 demonstrated significantly higher effectiveness as a pro-apoptotic drug than DOX. This was evident in the higher levels of markers of apoptosis, such as the externalization of phosphatidylserine and the elevated level of cytochrome c. An extension of incubation time led to an increase in intracellular calcium levels after treatment with DOX. Lower changes in the calcium content were associated with the influence of WP 631. DOX led to the activation of all tested caspases, 8, 9 and 3, whereas WP 631 only induced an increase in caspase 8 activity after 24h of treatment and consequently led to the cleavage of PARP. The lack of active caspase 3 had no outcome on the single and double-stranded DNA breaks. The obtained results show that WP 631 was considerably more genotoxic towards the investigated cell line than DOX. This effect was especially visible after longer times of incubation. The above detailed studies indicate that WP 631 generates early apoptosis and cell death independent of caspase-3, detected at relatively late time points. The observed differences in the mechanisms of the action of WP631 and DOX suggest that this bisanthracycline can be an effective alternative in ovarian cancer treatment.
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