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Title: 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 » 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.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [3];  [1];  [1];  [4];  [5]; ;  [6];  [7];  [8]
  1. Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan (China)
  2. Graduate School of Biotechnology and Bioinformatics, Yuan Ze University, Taoyuan, Taiwan (China)
  3. Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan (China)
  4. Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China)
  5. Department of Animal Science, National Chung Hsing University, Taichung, Taiwan (China)
  6. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan (China)
  7. Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China)
  8. 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}
}