Colorectal carcinoma cell targeting aromatherapy with Teucrium ramosissimum essential oil to sensitize TRAIL/Apo2L-induced HCT-116 cell death

This report drives insights for the investigation of the underlying mechanisms of antitumor effects of Teucrium ramosissimum (TrS) essential oil (EO) that elicits colon tumor protection via activation of cell death machinery. A study of the aerial part phytocomplex was performed by FTIR spectra and GC/MS. In vivo colon carcinogenesis induced by LPS was carried out using mouse model. HCT-116 cells were coincubated with TrS EO and TRAIL-resistant cancer cells, and then cell lysates were assessed using Western blotting technique for death and decoy receptor expression. TrS essential oil potentiates TRAIL-mediated apoptosis cell death of HCT-116 as detected by PARP cleavage and caspase activation. Further data suggest that TrS up-regulates DR 5/4 expression, and down-regulates DcRs expression. Additionally, TrS potentiates apoptosis in TRAIL-resistant tumor cells through induction of MAPK signalling components, including ERK, p38 kinase, JNK, and activation of CHOP, and SP1, involved in DR5 expression. Moreover, Teucrium EO phytoconstituents mediate HCT-116 cells apoptosis by evoking cell cycle arrest at the G1 and G2/M phase through diminishing the expression of cyclin D1 acting as a potent multitargeted factors of inhibition of JAK/STAT oncogenic signaling pathway. These results demonstrate that TRAIL-induced apoptosis enhancing effect of TrS mediated through proto-oncogene expression in HCT-116. TrS administered intragastrically is able to prevent tumor of colon by stopping carcinogenesis process and impede tumor cell growth in in vivo analysis promoted by LPS. On the whole, our results revealed that TrS is an effective antitcancer agent through the induction of transcription factor and kinases, either are needed to trigger Apo2L receptors.