Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells
Objective: Non-Small Cell Lung Cancer (NSCLC) is extremely lethal upon metastasis and requires safe and effective systemic therapies to improve a patient's prognosis. Prodigiosin (PG) appears to selectively and effectively target cancer but not healthy cells. However, PG's cancer-specific...
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sg-ntu-dr.10356-879962020-09-21T11:33:25Z Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells Davient, Bala Ng, Jessica Pei Zhen Xiao, Qiang Li, Liang Yang, Liang School of Biological Sciences Singapore Centre for Environmental Life Sciences Engineering Prodigiosin Small Molecule DRNTU::Science::Biological sciences Objective: Non-Small Cell Lung Cancer (NSCLC) is extremely lethal upon metastasis and requires safe and effective systemic therapies to improve a patient's prognosis. Prodigiosin (PG) appears to selectively and effectively target cancer but not healthy cells. However, PG's cancer-specific activity has remained elusive until recently. Methods: PG's cancer-specific performance was compared to Docetaxel (DTX), Paclitaxel (PTX), and Doxorubicin (DOX) against human lung adenocarcinoma (A549) and human small airway epithelial cells (HSAEC). Combination of PG with DTX, PTX, or DOX in a 1:1 ED50 ratio was also evaluated. MTT assay was used to determine the post-treatment cell viability. RNA-sequencing was used for comparative transcriptomics analysis between A549 and HSAEC treated with 1.0 μM PG for 24 h. Results: PG reduced A549 cell viability by four-folds greater than HSAEC. In comparison to DTX, PTX and DOX, PG was ~1.7 times more toxic toward A549, and 2.5 times more protective toward HSAEC. Combination of PG in a 1:1 ED50 ratio with DTX, PTX, or DOX failed to exhibit synergistic toxicity toward A549 or protection toward HSAEC. In A549, genes associated in DNA replication were downregulated, while genes directly or indirectly associated in lipid and cholesterol biogenesis were upregulated. In HSAEC, co-upregulation of oncogenic and tumor-suppressive genes was observed. Conclusion: An overactive lipid and cholesterol biogenesis could have caused A549's autophagy, while a balancing-act between genes of oncogenic and tumor-suppressive nature could have conferred HSAEC heightened survival. Overall, PG appears to be a smart chemotherapeutic agent that may be both safe and effective for NSCLC patients. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Published version 2018-12-18T02:21:28Z 2019-12-06T16:53:46Z 2018-12-18T02:21:28Z 2019-12-06T16:53:46Z 2018 Journal Article Davient, B., Ng, J. P. Z., Xiao, Q., Li, L., & Yang, L. (2018). Comparative Transcriptomics Unravels Prodigiosin's Potential Cancer-Specific Activity Between Human Small Airway Epithelial Cells and Lung Adenocarcinoma Cells. Frontiers in Oncology, 8, 573-. doi:10.3389/fonc.2018.00573 https://hdl.handle.net/10356/87996 http://hdl.handle.net/10220/47030 10.3389/fonc.2018.00573 en Frontiers in Oncology © 2018 Davient, Ng, Xiao, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. 13 p. application/pdf |
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Prodigiosin Small Molecule DRNTU::Science::Biological sciences Davient, Bala Ng, Jessica Pei Zhen Xiao, Qiang Li, Liang Yang, Liang Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
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Objective: Non-Small Cell Lung Cancer (NSCLC) is extremely lethal upon metastasis and requires safe and effective systemic therapies to improve a patient's prognosis. Prodigiosin (PG) appears to selectively and effectively target cancer but not healthy cells. However, PG's cancer-specific activity has remained elusive until recently.
Methods: PG's cancer-specific performance was compared to Docetaxel (DTX), Paclitaxel (PTX), and Doxorubicin (DOX) against human lung adenocarcinoma (A549) and human small airway epithelial cells (HSAEC). Combination of PG with DTX, PTX, or DOX in a 1:1 ED50 ratio was also evaluated. MTT assay was used to determine the post-treatment cell viability. RNA-sequencing was used for comparative transcriptomics analysis between A549 and HSAEC treated with 1.0 μM PG for 24 h.
Results: PG reduced A549 cell viability by four-folds greater than HSAEC. In comparison to DTX, PTX and DOX, PG was ~1.7 times more toxic toward A549, and 2.5 times more protective toward HSAEC. Combination of PG in a 1:1 ED50 ratio with DTX, PTX, or DOX failed to exhibit synergistic toxicity toward A549 or protection toward HSAEC. In A549, genes associated in DNA replication were downregulated, while genes directly or indirectly associated in lipid and cholesterol biogenesis were upregulated. In HSAEC, co-upregulation of oncogenic and tumor-suppressive genes was observed.
Conclusion: An overactive lipid and cholesterol biogenesis could have caused A549's autophagy, while a balancing-act between genes of oncogenic and tumor-suppressive nature could have conferred HSAEC heightened survival. Overall, PG appears to be a smart chemotherapeutic agent that may be both safe and effective for NSCLC patients. |
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School of Biological Sciences |
author_facet |
School of Biological Sciences Davient, Bala Ng, Jessica Pei Zhen Xiao, Qiang Li, Liang Yang, Liang |
format |
Article |
author |
Davient, Bala Ng, Jessica Pei Zhen Xiao, Qiang Li, Liang Yang, Liang |
author_sort |
Davient, Bala |
title |
Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
title_short |
Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
title_full |
Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
title_fullStr |
Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
title_full_unstemmed |
Comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
title_sort |
comparative transcriptomics unravels prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/87996 http://hdl.handle.net/10220/47030 |
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1681057496164204544 |