Plumbagin increases paclitaxel-induced cell death and overcomes paclitaxel resistance in breast cancer cells through ERK-mediated apoptosis induction
Anna Kawiak , Anna Domachowska , Ewa Łojkowska
AbstractERK is a component of mitogen-activated protein kinases that controls a range of cellular processes including cell proliferation and survival. The upregulation of ERK has been associated with apoptosis inhibition in response to various stimuli including chemotherapeutic agents. Research has suggested that the upregulation of ERK signaling by the anticancer agent paclitaxel leads to acquired resistance of cells to this compound. The presented research focused on determining the role of plumbagin, a naturally derived naphthoquinone, in the sensitization of breast cancer cells to paclitaxel-induced cell death and the involvement of ERK signaling in this process. The results of the study indicated that plumbagin increases the sensitivity of breast cancer cells to paclitaxel. Moreover, a synergistic effect between plumbagin and paclitaxel was observed. Plumbagin was shown to decrease levels of phosphorylated ERK in breast cancer cells and abrogated paclitaxel-induced ERK phosphorylation. The role of ERK in plumbagin-mediated sensitization of breast cancer cells to paclitaxel was shown through the enhancement of the synergistic effect between compounds in cells with decreased ERK expression. Furthermore, plumbagin reduced p-ERK levels in paclitaxel-resistant breast cancer cells and resensitized paclitaxel-resistant cells to this compound. These results imply that plumbagin inhibits ERK activation in breast cancer cells, which plays a role in the sensitization of cells to paclitaxel-induced cell death.
|Journal series||Journal of Natural Products, ISSN 0163-3864, (N/A 100 pkt)|
|Publication size in sheets||0.50|
|ASJC Classification||; ; ; ; ; ;|
|Score||= 100.0, 03-07-2020, ArticleFromJournal|
|Publication indicators||= 1.000; = 3.000; : 2018 = 1.521; : 2018 = 4.257 (2) - 2018=3.938 (5)|
|Citation count*||4 (2020-06-19)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.