Despite the rapid advances in chemotherapy regimens, the outcome of patients with breast cancer is not satisfactory. One of the reasons of this dissatisfaction is that subsets of cells in tumors which referred as cancer stem cells (CSCs) show and/or gain resistance to therapies. Thus, compounds that target CSCs are urgently needed. Since some are already used in the clinic, natural products have great potential for further development as anti cancer drugs. The aim of this study is to investigate the cytotoxic activity of tingenin b (or 22β-hydroxytingenone) which is a quinone-methide triterpenoid structurally related to tingenone, against breast CSCs (stem-cell enriched population from MCF-7 cell line, MCF-7s). It has been found that tingenin b was cytotoxic against MCF-7s (IC50 value for 48 h was found to be 2.38 μM) by inducing apoptosis. It was evident by Annexin V staining positivity, decreased mitochondrial membrane potential and Bcl-2 dephosphorylation with a concomitant increase in Bax protein expression. In addition, endoplasmic reticulum stress was also found to be involved in tingenin b-induced cell death. In conclusion, the results warrant further studies aimed at elucidating and corroborating its possible use in the treatment of breast cancer.

The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro / Cevatemre, Buse; Botta, Bruno; Mori, Mattia; Berardozzi, Simone; Ingallina, Cinzia; Ulukaya, Engin. - In: CHEMICO-BIOLOGICAL INTERACTIONS. - ISSN 0009-2797. - STAMPA. - 260:(2016), pp. 248-255. [10.1016/j.cbi.2016.10.001]

The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro

BOTTA, Bruno;MORI, MATTIA;BERARDOZZI, SIMONE;INGALLINA, CINZIA;
2016

Abstract

Despite the rapid advances in chemotherapy regimens, the outcome of patients with breast cancer is not satisfactory. One of the reasons of this dissatisfaction is that subsets of cells in tumors which referred as cancer stem cells (CSCs) show and/or gain resistance to therapies. Thus, compounds that target CSCs are urgently needed. Since some are already used in the clinic, natural products have great potential for further development as anti cancer drugs. The aim of this study is to investigate the cytotoxic activity of tingenin b (or 22β-hydroxytingenone) which is a quinone-methide triterpenoid structurally related to tingenone, against breast CSCs (stem-cell enriched population from MCF-7 cell line, MCF-7s). It has been found that tingenin b was cytotoxic against MCF-7s (IC50 value for 48 h was found to be 2.38 μM) by inducing apoptosis. It was evident by Annexin V staining positivity, decreased mitochondrial membrane potential and Bcl-2 dephosphorylation with a concomitant increase in Bax protein expression. In addition, endoplasmic reticulum stress was also found to be involved in tingenin b-induced cell death. In conclusion, the results warrant further studies aimed at elucidating and corroborating its possible use in the treatment of breast cancer.
2016
breast; chemotherapy; ER stress; malignancy; mammosphere; tingenone; antineoplastic agents; apoptosis; breast neoplasms; cell membrane; cell nucleus; cell proliferation; endoplasmic reticulum stress; humans; MCF-7 cells; maytenus; microscopy, fluorescence; mitochondria; neoplastic stem cells; phytotherapy; triterpenes; toxicology
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The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro / Cevatemre, Buse; Botta, Bruno; Mori, Mattia; Berardozzi, Simone; Ingallina, Cinzia; Ulukaya, Engin. - In: CHEMICO-BIOLOGICAL INTERACTIONS. - ISSN 0009-2797. - STAMPA. - 260:(2016), pp. 248-255. [10.1016/j.cbi.2016.10.001]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/961957
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