Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53
Abstract
Undecylprodigiosin (UP) is a bacterial bioactive metabolite produced by Streptomyces and Serratia. In this study, we explored the anticancer effect of UP. Human breast carcinoma cell lines BT-20, MCF-7, MDA-MB-231 and T47D and one nonmalignant human breast epithelial cell line, MCF-10A, were tested in this study. We found that UP exerted a potent cytotoxicity against all breast carcinoma cell lines in a dose- and time-dependent manner. In contrast, UP showed limited toxicity to MCF-10A cells, indicating UP's cytotoxic effect is selective for malignant cells. UP's cytotoxic effect was due to apoptosis, as confirmed by positive TUNEL signals, annexin V-binding, caspase 9 activation and PARP cleavage. Notably, UP-induced apoptosis was blocked by the pan-caspase inhibitor z-VAD.fmk, further indicating the involvement of caspase activity. Moreover, UP caused a marked decrease of the levels of antiapoptotic BCL-X{sub L}, Survivin and XIAP while enhancing the levels of proapoptotic BIK, BIM, MCL-1S and NOXA, consequently favoring induction of apoptosis. Additionally, we found that cells with functional p53 (MCF-7, T47D) or mutant p53 (BT-20, MDA-MB-231) were both susceptible to UP's cytotoxicity. Importantly, UP was able to induce apoptosis in MCF-7 cells with p53 knockdown by RNA interference, confirming the dispensability of p53 in UP-induced apoptosis. Overall,more »
- Authors:
-
- Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan (China)
- Graduate School of Biotechnology and Bioinformatics, Yuan Ze University, Taoyuan, Taiwan (China)
- Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan (China)
- Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China)
- Department of Animal Science, National Chung Hsing University, Taichung, Taiwan (China)
- Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan (China)
- Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China)
- Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China)
- Publication Date:
- OSTI Identifier:
- 21077879
- Resource Type:
- Journal Article
- Journal Name:
- Toxicology and Applied Pharmacology
- Additional Journal Information:
- Journal Volume: 225; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.08.007; PII: S0041-008X(07)00370-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ADP; APOPTOSIS; BORON CHLORIDES; CARCINOMAS; KETONES; MAMMARY GLANDS; POLYMERASES; RIBOSE; RNA; SERRATIA; STREPTOMYCES; TETRAZOLIUM; TIME DEPENDENCE; TOXICITY
Citation Formats
Ho, T -F, Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Department of Medical Technology, Central Taiwan University of Science and Technology, Taichung 40605, Taiwan, Ma, C -J, Lu, C -H, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, Tsai, Yo-Ting, Wei, Y -H, Chang, J -S, Lai, J -K, Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Cheuh, Pin-Ju, Yeh, C -T, Tang, P -C, Jingua, T C, Ko, J -L, Liu, F -S, and Yen, H E. Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53. United States: N. p., 2007.
Web. doi:10.1016/j.taap.2007.08.007.
Ho, T -F, Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Department of Medical Technology, Central Taiwan University of Science and Technology, Taichung 40605, Taiwan, Ma, C -J, Lu, C -H, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, Tsai, Yo-Ting, Wei, Y -H, Chang, J -S, Lai, J -K, Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Cheuh, Pin-Ju, Yeh, C -T, Tang, P -C, Jingua, T C, Ko, J -L, Liu, F -S, & Yen, H E. Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53. United States. https://doi.org/10.1016/j.taap.2007.08.007
Ho, T -F, Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Department of Medical Technology, Central Taiwan University of Science and Technology, Taichung 40605, Taiwan, Ma, C -J, Lu, C -H, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, Tsai, Yo-Ting, Wei, Y -H, Chang, J -S, Lai, J -K, Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Cheuh, Pin-Ju, Yeh, C -T, Tang, P -C, Jingua, T C, Ko, J -L, Liu, F -S, and Yen, H E. 2007.
"Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53". United States. https://doi.org/10.1016/j.taap.2007.08.007.
@article{osti_21077879,
title = {Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53},
author = {Ho, T -F and Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan and Department of Medical Technology, Central Taiwan University of Science and Technology, Taichung 40605, Taiwan and Ma, C -J and Lu, C -H and Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan and Tsai, Yo-Ting and Wei, Y -H and Chang, J -S and Lai, J -K and Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan and Cheuh, Pin-Ju and Yeh, C -T and Tang, P -C and Jingua, T C and Ko, J -L and Liu, F -S and Yen, H E},
abstractNote = {Undecylprodigiosin (UP) is a bacterial bioactive metabolite produced by Streptomyces and Serratia. In this study, we explored the anticancer effect of UP. Human breast carcinoma cell lines BT-20, MCF-7, MDA-MB-231 and T47D and one nonmalignant human breast epithelial cell line, MCF-10A, were tested in this study. We found that UP exerted a potent cytotoxicity against all breast carcinoma cell lines in a dose- and time-dependent manner. In contrast, UP showed limited toxicity to MCF-10A cells, indicating UP's cytotoxic effect is selective for malignant cells. UP's cytotoxic effect was due to apoptosis, as confirmed by positive TUNEL signals, annexin V-binding, caspase 9 activation and PARP cleavage. Notably, UP-induced apoptosis was blocked by the pan-caspase inhibitor z-VAD.fmk, further indicating the involvement of caspase activity. Moreover, UP caused a marked decrease of the levels of antiapoptotic BCL-X{sub L}, Survivin and XIAP while enhancing the levels of proapoptotic BIK, BIM, MCL-1S and NOXA, consequently favoring induction of apoptosis. Additionally, we found that cells with functional p53 (MCF-7, T47D) or mutant p53 (BT-20, MDA-MB-231) were both susceptible to UP's cytotoxicity. Importantly, UP was able to induce apoptosis in MCF-7 cells with p53 knockdown by RNA interference, confirming the dispensability of p53 in UP-induced apoptosis. Overall, our results establish that UP induces p53-independent apoptosis in breast carcinoma cells with no marked toxicity to nonmalignant cells, raising the possibility of its use as a new chemotherapeutic drug for breast cancer irrespective of p53 status.},
doi = {10.1016/j.taap.2007.08.007},
url = {https://www.osti.gov/biblio/21077879},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 225,
place = {United States},
year = {Sat Dec 15 00:00:00 EST 2007},
month = {Sat Dec 15 00:00:00 EST 2007}
}