SN38 increases IL-8 expression through the MAPK pathways in HCT8 cells

Abstract

The overexpression of interleukin-8 (IL-8) is closely associated with poor tumor differentiation, metastasis and tumor progression. This study aimed to examine the effects and mechanisms of action of SN38 (a metabolite of the camptothecin derivative, CPT-11) on IL-8 expression in HCT8 cells, using ELISA, CCK-8 and western blot analysis. Among jatrorrhizine, evodiamine, 5-fluorouracil and SN38, SN38 was found to inhibit the proliferation of HCT8 cells in a dose-dependent manner, but to increase IL-8 secretion from HCT8 cells. Of the other agents, evodiamine was found to inhibit both IL-8 secretion and cell proliferation, and jatrorrhizine was found to increase IL-8 secretion without any obvious inhibitory effect on cell proliferation. Further experiments revealed that the increased activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) by SN38 contributed to the decreased cell proliferation and to the overexpression of IL-8 induced by SN38. Our results suggested that the MAPK pathways are activated by SN38, resulting in the upregulation of IL-8 expression and in the inhibition of cell proliferation in an IL-8-independent manner. Thus, the potential benefit of the use of a combination of camptothecin-11 with other chemical drugs with inhibitory effects on IL-8 expression, should be paid more attention in treating colon cancer.

Interactions of a medicinal climber Tinospora cordifolia with supportive interspecific plants trigger the modulation in its secondary metabolic profiles

“…These alkaloids being dopamine receptors agonists activate trigeminal motoneurons that increase the muscle tone 44 . These compounds along-with above reported terpenoids, flavonoids and coumarin are also capable to modulate MAPK, ERK1, ERK2 and protein kinase A that are involved in signal transduction pathways to control the innate and adaptive immunity and cell death 45–47 . Cinnamaldehyde and sodium thiosalicylate along-with 20-hydroxyecdysone elevated in AIN group are known anti-inflammatory compounds and boost up immune system 48–50 .…”

Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer

“…However, this drug causes severe side effects, such as severe diarrhea and colitis, limiting dose intensification 8, 26. Treatment with SN38, which is the active metabolite of CPT-11, has been reported to produce inflammatory cytokines 27, 28. To examine whether nCUR shows anti-inflammatory activity, we used Raw264.7 cells and BMDMs in this experiment.…”

Irinotecan (CPT-11) Canonical Anti-Cancer Drug Can also Modulate Antiviral and Pro-Inflammatory Responses of Primary Human Synovial Fibroblasts

“…Indeed, it has been demonstrated that CPT and CPT-11 induce activation of the NF-κB pathway in a variety of human carcinoma cell lines, a mechanism thought to contribute to resistance to chemotherapy [41][42][43]. In addition, SN38, the active metabolite of CPT-11, has been shown to increase CXCL8 secretion by enhancing the phosphorylation of MAP kinases in HCT8 cells [44]. By contrast, Riedlinger et al evidenced that topoisomerase I inhibitors interfere with cytokine-induced and NF-κB p65-mediated inflammatory gene expression in a variety of cell lines [45].…”