Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System®) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38-1.75μM. It inhibited sphere formation at relatively lower doses (<1.56μM). Apoptosis was induced in MCF-7 and MCF-7s cells. In addition, extensive cytoplasmic vacuolation was observed, implying an incompleted autophagy as evidenced by the increase of autophagy-related proteins (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdcscid/J mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows cytotoxic activity on breast cancer both in vitro and in vivo. It seems to represent a robust promising agent for the treatment of breast cancer. Pristimerin's itself or synthetic novel derivatives should be taken into consideration for novel potent anticancer agent(s).

A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer / Cevatemre, B.; Erkısa, M.; Aztopal, N.; Karakas, D.; Alper, P.; Tsimplouli, C.; Sereti, E.; Dimas, K.; Armutak, E. I. I.; Gurevin, E. G.; Uvez, A.; Mori, M.; Berardozzi, S.; Ingallina, C.; D'Acquarica, I.; Botta, B.; Ozpolat, B.; Ulukaya, E.. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 129:(2018), pp. 500-514. [10.1016/j.phrs.2017.11.027]

A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer

Berardozzi S.;Ingallina C.;D'Acquarica I.;Botta B.;
2018

Abstract

Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System®) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38-1.75μM. It inhibited sphere formation at relatively lower doses (<1.56μM). Apoptosis was induced in MCF-7 and MCF-7s cells. In addition, extensive cytoplasmic vacuolation was observed, implying an incompleted autophagy as evidenced by the increase of autophagy-related proteins (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdcscid/J mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows cytotoxic activity on breast cancer both in vitro and in vivo. It seems to represent a robust promising agent for the treatment of breast cancer. Pristimerin's itself or synthetic novel derivatives should be taken into consideration for novel potent anticancer agent(s).
cytoplasmic vacuolation; endoplasmic reticulum stress; mammosphere; triterpenoid
01 Pubblicazione su rivista::01a Articolo in rivista
A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer / Cevatemre, B.; Erkısa, M.; Aztopal, N.; Karakas, D.; Alper, P.; Tsimplouli, C.; Sereti, E.; Dimas, K.; Armutak, E. I. I.; Gurevin, E. G.; Uvez, A.; Mori, M.; Berardozzi, S.; Ingallina, C.; D'Acquarica, I.; Botta, B.; Ozpolat, B.; Ulukaya, E.. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 129:(2018), pp. 500-514. [10.1016/j.phrs.2017.11.027]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1086554
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