Research Paper Volume 13, Issue 18 pp 21975—21990

Thymus hirtus sp. algeriensis Boiss. and Reut. volatile oil enhances TRAIL/Apo2L induced apoptosis and inhibits colon carcinogenesis through upregulation of death receptor pathway

Fatma Guesmi1,2, , Sahdeo Prasad1,3, , Manel Ben Ali4, , Ismail A. Ismail4, , Ahmed Landoulsi2, ,

  • 1 Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
  • 2 Laboratory of Biochemistry and Molecular Biology, University of Carthage, Faculty of Sciences of Bizerte, Zarzouna, Bizerte 7021, Tunisia
  • 3 Research and Development, Noble Pharma LLC, Menomonie, WI 54751, USA
  • 4 Department of Biology, College of Science, Taif University, Taif 21944, Saudi Arabia

Received: January 11, 2021       Accepted: August 11, 2021       Published: September 20, 2021      

https://doi.org/10.18632/aging.203552
How to Cite

Copyright: © 2021 Guesmi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: The aim of the study is to determine the anticancer activity of Thymus algeriensis (TS) and its underlying mechanisms using in vitro and in animal models.

Methods: HCT116 cells were treated with TS essential oil alone or with TRAIL, and then its anticancer effect was determined by using MTT assay, live dead assay, caspase activation and PARP cleavage. Further mechanisms of its anticancer effects was determined by analyzing expression of death receptor signaling pathway using Western blotting. A mouse model was also used to assess the antitumor potential of thyme essential oil.

Results: TS oily fraction showed tumor growth inhibitory effect even at lower concentration. TS induces apoptotic cell death as indicated by cleavage of PARP, and activation of the initiator and effector caspases (caspase-3, -8 and -9). Further, results showed that TS increases the expression of death receptors (DRs) and reduces the expression of TRAIL decoy receptors (DcRs). In addition, upregulation of signaling molecules of MAPK pathway (p38 kinase, ERK, JNK), down-regulation of c-FLIP, and overexpression of SP1 and CHOP were observed by TS. Further in animal model, intragastric administration of TS (12.5 mg/ml and 50 mg/ml) prevented colorectal carcinogenesis by blocking multi-steps in carcinoma.

Conclusion: Overall, these results indicate that thymus essential oil promotes apoptosis in HCT116 cells and impedes tumorigenesis in animal model. Moreover, thyme potentiates TRAIL-induced cell death through upregulation of DRs, CHOP and SP1 as well as downregulation of antiapoptotic proteins in HCT116 cells. However, therapeutic potential of TS needs to be further explored.

Abbreviations

SDS-PAGE: SDS-Polyacrylamide gel electrophoresis; PBS-T: Phosphate-buffered saline-Tween; DMEM: Dulbecco’s minimum essential medium; DcR: Decoy receptor; DR: death receptor; FLICE: FADD-like interleukin-1b converting enzyme; MAPKs: mitogen-activated protein kinases; PAGE: polyacrylamide gel electrophoresis; PI: Propidium Iodide; PBS: phosphate buffered saline.