Andrographolide Enhances TRAIL-Induced Apoptosis via <i>p53</i>-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells

Deng, Yuyou; Bi, Ran; Guo, Haoran; Yang, Jiaxin; Du, Yujun; Wang, Chunxi; Wei, Wei

doi:10.7150/ijbs.30847

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Int J Biol Sci 2019; 15(3):688-700. doi:10.7150/ijbs.30847 This issue Cite

Research Paper

Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells

Yuyou Deng^1,2, Ran Bi^1,2, Haoran Guo², Jiaxin Yang², Yujun Du³, Chunxi Wang^1✉, Wei Wei^2✉

1. Department of Urology, The First Hospital of Jilin University, Changchun, Jilin Province 130021, China.
2. Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin Province 130021, China.
3. Department of Nephrology, First Hospital of Jilin University, Changchun, Jilin Province 130021, China.

Citation:

Deng Y, Bi R, Guo H, Yang J, Du Y, Wang C, Wei W. Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells. Int J Biol Sci 2019; 15(3):688-700. doi:10.7150/ijbs.30847. https://www.ijbs.com/v15p0688.htm

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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective chemotherapeutic agent that specifically impairs cancer cells while sparing normal cells; however, some cancer cells develop resistance to TRAIL. Here, we identified Andrographolide, a diterpenoid lactone derived from a traditional herbal medicine Andrographis paniculata, as an ideal sensitizer for TRAIL to overcome bladder cancer. Our results showed that combination treatment of Andro and TRAIL retarded growth, attenuated proliferation, decreased colony formation, inhibited migration and promoted caspases-mediated apoptosis in T24 cells. Additionally, the sensitization by Andro is achieved through up-regulation of death receptors (DR4 and DR5) of TRAIL in a p53-dependent manner. Crucially, Andro is also capable of inactivating NF-κB signaling pathway via transcriptional down-regulation p65/RelA, which is further contributed to enhancement of TRAIL-mediated cytotoxicity. These results indicated that non-toxic doses of Andrographolide sensitized bladder cancer cells to TRAIL-mediated apoptosis, suggesting it as an effective therapeutic agent for TRAIL resistant human bladder cancers.

Keywords: andrographolide, bladder cancer, death receptors, TRAIL, NF-κB

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APA

Deng, Y., Bi, R., Guo, H., Yang, J., Du, Y., Wang, C., Wei, W. (2019). Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells. International Journal of Biological Sciences, 15(3), 688-700. https://doi.org/10.7150/ijbs.30847.

ACS

Deng, Y.; Bi, R.; Guo, H.; Yang, J.; Du, Y.; Wang, C.; Wei, W. Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells. Int. J. Biol. Sci. 2019, 15 (3), 688-700. DOI: 10.7150/ijbs.30847.

NLM

CSE

Deng Y, Bi R, Guo H, Yang J, Du Y, Wang C, Wei W. 2019. Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells. Int J Biol Sci. 15(3):688-700.

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