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  • Violacein anticancer activity is enhanced under hypoxia

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    Author(s)
    Hashimi, Saeed M
    Xu, Tiefeng
    Wei, Ming Q
    Griffith University Author(s)
    Hashimi, Saeed M.
    Wei, Ming Q.
    Year published
    2015
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    Abstract
    Current cancer treatments of solid tumours such as chemotherapy and radiotherapy, have yet to produce effective therapeutic results due to non-specific targeting. This has led to many complications, such as toxicities in cancer patients. The ability of natural compounds in inducing programmed cell death (apoptosis), a process dysregulated in cancer cells, has been extensively studied in recent studies. This study assessed the anti-proliferative activity of violacein in a number of human cancer cell lines under normal and hypoxic conditions. Furthermore, we investigated its effects in a tumour‑bearing subcutaneous mouse model. ...
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    Current cancer treatments of solid tumours such as chemotherapy and radiotherapy, have yet to produce effective therapeutic results due to non-specific targeting. This has led to many complications, such as toxicities in cancer patients. The ability of natural compounds in inducing programmed cell death (apoptosis), a process dysregulated in cancer cells, has been extensively studied in recent studies. This study assessed the anti-proliferative activity of violacein in a number of human cancer cell lines under normal and hypoxic conditions. Furthermore, we investigated its effects in a tumour‑bearing subcutaneous mouse model. We also examined the ability of a tumour‑targeting Salmonella strain to produce violacein for local delivery within the tumour microenvironment. The results showed that hypoxia significantly increased the cytotoxic effects of violacein. The most significant reduction in the IC50 was in the HT29 (12.6-fold) and HCT116 (4.8-fold) colon cancer cell lines, HN5 head and neck squamous carcinoma cell line (6.5-fold), and MCF-7 breast ductal carcinoma cell line (4-fold). Among the cell lines tested for active caspase-3/7 activity, violacein only increased caspase-3/7 activity in the A549 non-small lung cancer cell line. In vivo efficacy of violacein showed that HN5 tumour‑bearing mice had regressed tumours during the treatment period and survival increased. The results also showed that transfer of the violacein biosynthetic cluster into the oncolytic strain VNP20009 of Salmonella resulted in the production of active violacein, suggesting targeted delivery of violacein by VNP20009. Taken together, our study has shown that hypoxia synergises the effects of violacein and the results from the in vivo administration of violacein require further investigation of violacein as an anticancer chemotherapeutic.
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    Journal Title
    Oncology Reports
    Volume
    33
    Issue
    4
    Publisher URI
    https://www.spandidos-publications.com/or/33/4/1731
    DOI
    https://doi.org/10.3892/or.2015.3781
    Copyright Statement
    © The Author(s) 2015. This is an open access article distributed under the terms of Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Oncology and Carcinogenesis not elsewhere classified
    Oncology and Carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/125012
    Collection
    • Journal articles

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