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https://doi.org/10.3390/cancers10110427
Title: | Ophiopogonin D, a steroidal glycoside abrogates STAT3 signaling cascade and exhibits anti-cancer activity by causing GSH/GSSG imbalance in lung carcinoma | Authors: | Lee, J.H Kim, C Lee, S.-G Sethi, G Ahn, K.S |
Keywords: | caspase glutathione glutathione disulfide glycoside ophiopogonin d STAT3 protein unclassified drug animal experiment animal model animal tissue antineoplastic activity apoptosis Article cancer inhibition controlled study drug effect drug inhibition drug mechanism enzyme activation female gene gene expression human human cell mouse non small cell lung cancer nonhuman oxidative stress signal transduction |
Issue Date: | 2018 | Citation: | Lee, J.H, Kim, C, Lee, S.-G, Sethi, G, Ahn, K.S (2018). Ophiopogonin D, a steroidal glycoside abrogates STAT3 signaling cascade and exhibits anti-cancer activity by causing GSH/GSSG imbalance in lung carcinoma. Cancers 10 (11) : 427. ScholarBank@NUS Repository. https://doi.org/10.3390/cancers10110427 | Rights: | Attribution 4.0 International | Abstract: | Natural medicinal plants are multi-targeted in nature and their anti-cancer activities are also complex and varied, thus requiring a more systematic analysis of their modes of action. Since the activation of signal transducer and activator of transcription 3 (STAT3) is often deregulated in non-small cell lung carcinoma (NSCLC) cells and tissue specimens, its negative regulation can form the basis for identification of targeted therapy. In this report, we analyzed the possible anti-cancer effects of ophiopogonin D (OP-D) and the underlying mechanisms by which OP-D exerts its actions in NSCLC. OP-D exhibited substantial suppressive activity on STAT3 signaling and this effect was found to be mediated via oxidative stress phenomena caused by disturbance in GSH/GSSG ratio. In addition, OP-D induced apoptosis, activated caspase mediated apoptotic cascade and decreased expression of various oncogenic genes. Consistently, OP-D treatment significantly reduced NSCLC tumor growth in preclinical mouse model with via decreasing levels of p-STAT3. OP-D was also found to attenuate the expression of STAT3-regulated anti-apoptosis, cell cycle regulator, and angiogenesis biomarkers. Our findings suggest that OP-D can induce apoptosis and exert anti-tumor effects by inhibition of STAT3 signaling pathways in NSCLC. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. | Source Title: | Cancers | URI: | https://scholarbank.nus.edu.sg/handle/10635/177833 | ISSN: | 20726694 | DOI: | 10.3390/cancers10110427 | Rights: | Attribution 4.0 International |
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