Thymol suppressed tumor growth in vitro and in vivo through inducing calcium overload in colorectal cancer

Background: Thymol, a bioactive phenolic compound, has proven to possess multiple anti-cancer activities, yet the function and underlying mechanism in colorectal Cancer (CRC) remain unclear.

Objectives: To shed light on the possible therapeutic effects of thymol in CRC based on calcium homeostasis regulation, and seek to explore the molecular pathways of calcium overload in the thymol-induced anti-CRC activity.

Methods: The effects of thymol on cell proliferation, viability, Apoptosis, anti-inflammatory effects, and calcium overload phenotype were investigated in HCT116 and CT26 cells. In addition, the in vivo therapeutic efficacies of thymol on CT26 xenograft tumor were also researched. Furthermore, molecular mechanisms of thymol-induced calcium overload were detected by Western blot, RT-qPCR, and immunofluorescence assays.

Results: We demonstrated that thymol significantly inhibited the proliferation, viability, and induced Apoptosis of HCT116 and CT26 cells. And, thymol suppressed the secretion of inflammatory factors. Furthermore, thymol promoted cell damage mediated by increased mitochondrial membrane potential in both two cells. In addition, thymol triggered the energy metabolism inhibition induced by calcium overload in HCT116 and CT26 cells. Besides, in vivo experiments based on CT26 xenograft tumor model also validated the positive anti-CRC activities.

Conclusions: Thymol inhibits CRC partially through inducing calcium overload, which provides an innovative solution for developing anti-CRC drugs.

calcium overload; colorectal cancer; energy metabolism; mitochondrion; thymol; xenograft tumor.