Article ; Online: Parthenolide inhibits proliferation and invasion, promotes apoptosis, and reverts the cell-cell adhesion loss through downregulation of NF-κB pathway TNF-α-activated in colorectal cancer cells.
2023 Volume 47, Issue 9, Page(s) 1638–1649
Abstract: The activation of the nuclear factor-κB (NF-κB) pathway has been associated with the development and progression of colorectal cancer (CRC). Parthenolide (PTL), a well-known inhibitor of the NF-κB pathway, has emerged as an alternative treatment. However, ...
| Abstract | The activation of the nuclear factor-κB (NF-κB) pathway has been associated with the development and progression of colorectal cancer (CRC). Parthenolide (PTL), a well-known inhibitor of the NF-κB pathway, has emerged as an alternative treatment. However, whether PTL activity is tumor cell-specific and dependent on the mutational background has not been defined. This study investigated the antitumor role of PTL after tumor necrosis factor-α (TNF-α) stimulation in various CRC cell lines with different mutational statuses of TP53. We observed that CRC cells displayed different patterns of basal p-IκBα levels; PTL reduced cell viability according to p-IκBα levels and p-IκBα levels varied among the cell lines according to the time of TNF-α stimulation. High concentrations of PTL reduced more effectively p-IκBα levels than low doses of PTL. However, PTL increased total IκBα levels in Caco-2 and HT-29 cells. In addition, PTL treatment downregulated p-p65 levels in HT-29 and HCT-116 cells stimulated by TNF-α in a dose-dependent manner. Moreover, PTL induced cell death via apoptosis and reduced the proliferation rate of TNF-α-treated HT-29 cells. Finally, PTL downregulated the messenger RNA levels of interleukin-1β, a downstream cytokine of NF-κB, reverted the E-cadherin-mediated disorganization of cell-cell contacts, and decreased the invasion of HT-29 cells. Together, these results suggest a differential antitumoral activity of PTL on CRC cells with different mutational statuses of TP53, modulating cell death, survival, and proliferation underlying the NF-κB pathway TNF-α-induced. Therefore, PTL has emerged as a potential treatment for CRC in an inflammatory NF-κB-dependent manner. |
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| MeSH term(s) | Humans ; NF-kappa B/metabolism ; NF-KappaB Inhibitor alpha/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Down-Regulation ; Cell Adhesion ; Caco-2 Cells ; Apoptosis ; Cell Proliferation ; Colorectal Neoplasms/drug therapy |
| Chemical Substances | NF-kappa B ; NF-KappaB Inhibitor alpha (139874-52-5) ; Tumor Necrosis Factor-alpha ; parthenolide (2RDB26I5ZB) |
| Language | English |
| Publishing date | 2023-06-20 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 1143453-3 |
| ISSN | 1095-8355 ; 1065-6995 |
| ISSN (online) | 1095-8355 |
| ISSN | 1065-6995 |
| DOI | 10.1002/cbin.12060 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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