LMU researchers have recognized a signaling pathway by way of which curcumin can suppress the metastasis of colorectal most cancers cells.
Colorectal most cancers is without doubt one of the commonest kinds of most cancers worldwide. In over half of all instances, an vital protecting mechanism in cells is inactivated by mutations – the tumor suppressor gene p53. The product of this gene, a transcription issue, induces a microRNA molecule referred to as miR-34, which performs a crucial position in tumor suppression. A workforce led by Heiko Hermeking, Professor of Experimental and Molecular Pathology at LMU, has now demonstrated in cell cultures and in a mouse mannequin that curcumin, a pure substance discovered within the spice turmeric, can bridge this silenced protecting mechanism by activating another, particular signaling pathway that induces the expression of miR-34.
There have been already indications within the literature that curcumin can induce miR-34, however there was no systematic investigation of the phenomenon prior to now. Furthermore, it was unclear what mechanism could possibly be behind it.”
Heiko Hermeking, Professor of Experimental and Molecular Pathology at LMU
Utilizing genetically-modified human colorectal most cancers cell traces, the researchers have now demonstrated that curcumin will increase the manufacturing of so-called reactive oxygen species (ROS) in tumor cells. These ROS activate a signaling pathway that results in the manufacturing of miR-34 by way of the transcription issue NRF2 – which then induces untimely growing older of the tumor cells and programmed cell loss of life. “Moreover, the flexibility of tumor cells emigrate and invade into surrounding tissue is impaired,” says Hermeking. “We have been additionally in a position to affirm in our mouse mannequin that the curcumin-induced expression of miR-34 suppresses the metastasis of colorectal most cancers cells into the lung.” As well as, curcumin made tumor cells extra delicate to the chemotherapeutic substance 5-FU via miR-34.
An vital facet of the outcomes is that these results are unbiased of p53, which is commonly misplaced within the majority of tumor sorts and could be troublesome to reconstitute in all tumor cells. “With curcumin, we have discovered a substance with which we might intervene within the sign cascade beneath p53 by activating miR-34,” says Hermeking. In response to the authors, the outcomes of the research might give rise to attention-grabbing approaches for brand new therapeutic choices, which ought to be pursued in additional research.
Liu, C., et al. (2023). Curcumin prompts a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal most cancers metastasis. Cell Loss of life & Differentiation. doi.org/10.1038/s41418-023-01178-1.