Abstract
Background and objectives: Mounting evidence shows that curcumin, a bioactive substance originating from turmeric root, has anticancer properties. Additionally, curcumin prevents the migration and metastasis of tumor cells. However, the molecular mechanism involved in the anti-metastatic action of curcumin is not clear. Most studies have suggested that migration inhibition is related to curcumin’s anti-inflammatory properties. Curcumin possesses a regulatory effect on insulin and insulin-like growth factor-1 (IGF-1) receptors and signaling. Insulin signaling is one of the important pathways involved in tumor initiation and progression; therefore, we proposed that the anti-metastatic effect of curcumin may mediate the downregulation of insulin and insulin-like growth factor-1 receptors. Materials and Methods: Viable resistant cells resulting from treating SW480 cells with 5-fluorouracil (5-FU) were subjected to curcumin treatment to analyze the proliferation and migration capacity in comparison to the untreated counterparts. To test the proliferation and migration potential, MTT, colony formation, and wound healing assays were performed. Real-time polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of insulin-like growth factor-1R (IGF-1R), insulin receptor (IR), and avian myelocytomatosis virus oncogene cellular homolog (MYC). Results: Our findings showed that curcumin significantly decreased insulin and IGF-1 receptors in addition to MYC expression. Additionally, the downregulation of the insulin and insulin-like growth factor-1 receptors was correlated to a greater decrease in the proliferation and migration of chemoresistant colorectal cancer cells. Conclusions: These results suggest the possible therapeutic effectiveness of curcumin in adjuvant therapy in metastatic colorectal cancer.
Highlights
Colorectal cancer is the third most common cancer and cause of death from cancer worldwide [1].Metastasis, drug resistance, and cancer recurrence are the major causes of colorectal mortality
The development of new treatments that target a subpopulation of tumor cells involved in metastasis, which are resistant to conventional therapy, could be an effective step
We found that curcumin reduced the expression of myelocytomatosis virus oncogene cellular homolog (MYC), insulin, and insulin-like growth factor-1 (IGF-1) receptors
Summary
Colorectal cancer is the third most common cancer and cause of death from cancer worldwide [1].Metastasis, drug resistance, and cancer recurrence are the major causes of colorectal mortality. The development of new treatments that target a subpopulation of tumor cells involved in metastasis, which are resistant to conventional therapy, could be an effective step. Curcumin prevents the migration and metastasis of tumor cells. Curcumin possesses a regulatory effect on insulin and insulin-like growth factor-1 (IGF-1) receptors and signaling. Insulin signaling is one of the important pathways involved in tumor initiation and progression; we proposed that the anti-metastatic effect of curcumin may mediate the downregulation of insulin and insulin-like growth factor-1 receptors. The downregulation of the insulin and insulin-like growth factor-1 receptors was correlated to a greater decrease in the proliferation and migration of chemoresistant colorectal cancer cells. Conclusions: These results suggest the possible therapeutic effectiveness of curcumin in adjuvant therapy in metastatic colorectal cancer
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