CGF induces ROS-mediated metabolic reprogramming and mitochondrial dysfunction to suppress colorectal cancer...

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Colorectal cancer (CRC) is a significant cause of cancer mortality worldwide.
• Effective therapeutic strategies for CRC are urgently needed.
• Natural compounds are being explored for their potential antitumor properties.

Purpose of the Study:

• To investigate the antitumor properties and underlying mechanism of Cya-Gly-Fer (CGF), a natural anthocyanin derivative, in colorectal cancer.
• To elucidate how CGF affects tumor growth, metastasis, and cellular metabolism.

Main Methods:

• Utilized colorectal cancer (CRC) cell lines, organoids, and xenograft models.
• Performed integrated transcriptomics and metabolomics analyses.
• Investigated the effects of CGF on central carbon metabolism, oxidative phosphorylation, ABC transporters, and signaling pathways.

Main Results:

• CGF significantly inhibited tumor growth and metastasis in preclinical models.
• CGF disrupted central carbon metabolism and oxidative phosphorylation.
• CGF induced intracellular ATP accumulation by downregulating ABC transporters, leading to mitochondrial dysfunction, excessive ROS generation, and suppression of the MAPK/ERK1/2/c-MYC signaling axis.
• CGF triggered cell-cycle arrest and apoptosis in CRC cells.

Conclusions:

• CGF exhibits potent antitumor properties against colorectal cancer.
• CGF functions by targeting mitochondrial homeostasis and inducing metabolic stress.
• CGF represents a promising therapeutic candidate for halting colorectal cancer progression.