Piperlongumine inhibits cancer stem cell properties and regulates multiple malignant phenotypes in oral cancer

Abstract

Abstract. Piperlongumine (PL), a natural product ofPiper longum, inhibits multiple malignant phenotypes. Therefore, the present study examined whether PL suppresses cancer stemness in oral cancer. The cellular effects of PL were determined by examining alterations in tumor sphere formation, cell migration, invasion, proliferation ability, chemosensitivity and radiosensitivity. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were performed in order to determine molecular expression levels. The present study revealed that PL inhibited cancer stem cell-forming ability and suppressed the expression of the stemness-related transcription factors SRY-Box 2, POU class 5 homeobox 1, and Nanog homeobox. However, it increased the expression of the differentiation marker cytokeratin 18. PL also suppressed cell migration and invasion, resulting in the elimination of the epithelial-mesenchymal transition. Furthermore, PL increased chemo-and radiosensitivity and suppressed tumor growth in vitro and in vivo. The results of the present study suggested that PL inhibits malignant phenotypes via the suppression of cancer stemness in oral cancer. Thus, PL may serve as an effective therapeutic agent for oral cancer.

The effect of piperlongumine on endothelial and lung adenocarcinoma cells with regulated expression of profilin-1

“… 19 Likewise, Chen et al have reported that the oral cancer cells after PL treatment were characterized by a decrease in the vimentin expression level. 18 In our study, the cells with lower level of PFN1 presented a strong reorganization of vimentin network and changes in the F-actin levels which were connected with alteration of PFN1 expression. In the case of cancer cells with a high degree of aggressiveness, the changes in morphology, cell adhesion, and the cytoskeletal proteins are very important in the context of cell migration.…”

“…Literature have reported that PL suppresses migration in a different type of cancer including oral cancer, bladder, glioma, and hepatocellular carcinomas. 18 , 1 , 65 , 66 Our results clearly showed that the downregulation of PFN1 expression in lung adenocarcinoma A549 cells inhibited their migration. Moreover, the treatment with PL enhanced this effect, what is confirmed by the fact that transfected cells without PL covered the scratch wound slower than untreated A549 cells with a naïve level of PFN1.…”

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

“…This indicates that piplartine plus auranofin is able to eliminate CRC‐SCs. Interestingly, piplartine also inhibited stemness properties in leukemia [ 223 ] and oral cancer [ 224 ] and had less effect on the viability of normal cells [ 213 , 214 ].…”

The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer

“…Furthermore, Gagat et al reported that treatments with 2-µM and 4-µM PL in A549 cells caused changes in the actin cytoskeleton [68]. In turn, a reduction in the level of vimentin was observed in PL-treated oral cancer cells (CGHNC8) [69]. The combination of the alkaloids used in this study caused an enhancement in the reorganization of the vimentin, actin and microtubule networks, which is probably associated with an increase in the cytotoxic effects of the alkaloids, as well as changes at the level of A549 cell proliferation and death.…”