Newswise — Colorectal cancer ranks among the prevalent cancer types worldwide. Mutations commonly deactivate a vital defense mechanism within cells, known as the tumor suppressor gene p53, in more than half of the cases. The gene's resultant product, a transcription factor, triggers the emergence of a microRNA molecule called miR-34, which plays a pivotal part in suppressing tumors. Under the guidance of Heiko Hermeking, a Professor of Experimental and Molecular Pathology at LMU, a team has now proven that curcumin, an inherent compound found in the spice turmeric, can revive this repressed protective mechanism. Curcumin achieves this by stimulating a distinct, alternative signaling pathway that prompts the expression of miR-34, as demonstrated in cell cultures and a mouse model.

"The existing literature hinted at the potential of curcumin to stimulate miR-34," Hermeking explains, "but a comprehensive investigation of this phenomenon was lacking, and the underlying mechanism remained unclear." By utilizing genetically-modified human colorectal cancer cell lines, the researchers have now illustrated that curcumin elevates the production of reactive oxygen species (ROS) within tumor cells. These ROS activate a signaling pathway that triggers the generation of miR-34 through the involvement of the transcription factor NRF2. Consequently, premature aging and programmed cell death are induced in the tumor cells. Hermeking adds, "Moreover, the migratory and invasive capabilities of tumor cells into neighboring tissue are impaired." The team also confirmed, using a mouse model, that curcumin-induced miR-34 expression suppresses the metastasis of colorectal cancer cells to the lungs. Additionally, curcumin rendered the tumor cells more receptive to the chemotherapeutic agent 5-FU, thanks to the involvement of miR-34.

A crucial aspect of the findings is that these effects occur irrespective of p53, which is frequently inactivated in most tumor types and challenging to restore in all tumor cells. Hermeking states, "Curcumin provides us with a substance through which we can intervene in the signaling pathway downstream of p53 by activating miR-34." The authors believe that the study results hold promise for exploring novel therapeutic possibilities, which should be further explored in subsequent studies. This discovery opens up intriguing avenues for the development of new treatment approaches.

Journal Link: Nature

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