Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-κB

  • Authors:
    • Chutima Kaewpiboon
    • Ratakorn Srisuttee
    • Waraporn Malilas
    • Jeong Moon
    • Sirichat Kaowinn
    • Il-Rae Cho
    • Randal N. Johnston
    • Wanchai Assavalapsakul
    • Young-Hwa Chung
  • View Affiliations

  • Published online on: November 12, 2013     https://doi.org/10.3892/or.2013.2844
  • Pages: 161-168
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Since multidrug resistance (MDR) is one of the main reasons for failure in cancer treatment, its suppression may increase the efficacy of cancer therapy. In the present study we attempted to identify a new and effective anticancer drug against MDR cancer cells. We first found that lung cancer A549 cells resistant to etoposide (A549RT-eto) exhibit upregulation of NF-κB and SIRT1 in comparison to A549 parental cells. During a search for anticancer drug candidates from medicinal plant sources, we found that an extract fraction (F14) of Bryophyllum laetivirens leaves downregulated expression of NF-κB and SIRT1, sensitizing the levels of A549RT-eto cells to apoptosis through downregulation of P-glycoprotein (P-gp), which is encoded by the MDR1 gene. To address whether NF-κB is involved in resistance to etoposide through P-gp, we treated A549RT-eto cells with Bay11-7802, an inhibitor of NF-κB. We then observed that Bay11-7802 treatment reduced P-gp expression levels, and furthermore combined treatment with the F14 extract and Bay11-7802 accelerated apoptosis through a decrease in P-gp levels, suggesting that NF-κB is involved in MDR. To address whether upregulation of SIRT1 is involved in resistance to etoposide through P-gp, we treated A549RT-eto cells with SIRT1 siRNA or nicotinamide (NAM), an inhibitor of SIRT1. we found that suppression of SIRT1 did not reduce P-gp levels. furthermore, the combined treatment with the F14 extract, and SIRT1 siRNA or NAM did not accelerate apoptosis, indicating that SIRT1 is not involved in the regulation of P-gp levels in A549RT-eto cells. Taken together, we suggest that upregulation of NF-κB determines etoposide resistance through P-gp expression in human A549 lung cancer cells. We herein demonstrated that B. laetivirens extract reverses etoposide resistance in human A549 lung cancer cells through downregulation of NF-κB.
View Figures
View References

Related Articles

Journal Cover

2014-January
Volume 31 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kaewpiboon C, Srisuttee R, Malilas W, Moon J, Kaowinn S, Cho I, Johnston RN, Assavalapsakul W and Chung Y: Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-κB. Oncol Rep 31: 161-168, 2014
APA
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Kaowinn, S., Cho, I. ... Chung, Y. (2014). Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-κB. Oncology Reports, 31, 161-168. https://doi.org/10.3892/or.2013.2844
MLA
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Kaowinn, S., Cho, I., Johnston, R. N., Assavalapsakul, W., Chung, Y."Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-κB". Oncology Reports 31.1 (2014): 161-168.
Chicago
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Kaowinn, S., Cho, I., Johnston, R. N., Assavalapsakul, W., Chung, Y."Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-κB". Oncology Reports 31, no. 1 (2014): 161-168. https://doi.org/10.3892/or.2013.2844