Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging. This review aims to summarize recent progress on the study of natural phenolic compounds in ameliorating CRC using in vivo models. This review followed the guidelines of the Preferred Reporting Items for Systematic Reporting and Meta-Analysis. Information on the relevant topic was gathered by searching the PubMed, Scopus, ScienceDirect, and Web of Science databases using keywords, such as “colorectal cancer” AND “phenolic compounds”, “colorectal cancer” AND “polyphenol”, “colorectal cancer” AND “phenolic acids”, “colorectal cancer” AND “flavonoids”, “colorectal cancer” AND “stilbene”, and “colorectal cancer” AND “lignan” from the reputed peer-reviewed journals published over the last 20 years. Publications that incorporated in vivo experimental designs and produced statistically significant results were considered for this review. Many of these polyphenols demonstrate anti-CRC activities by inhibiting key cellular factors. This inhibition has been demonstrated by antiapoptotic effects, antiproliferative effects, or by upregulating factors responsible for cell cycle arrest or cell death in various in vivo CRC models. Numerous studies from independent laboratories have highlighted different plant phenolic compounds for their anti-CRC activities. While promising anti-CRC activity in many of these agents has created interest in this area, in-depth mechanistic and well-designed clinical studies are needed to support the therapeutic use of these compounds for the prevention and treatment of CRC.

Current anti-breast cancer therapies often cause severe toxicity to normal cells and promote chemoresistance, while their exorbitant costs limit their accessibility to many patients. This underscores the need for safer, effective, and affordable alternative treatment strategies. In this study, we evaluated the anti-breast cancer potential of an alkaloid-rich dichloromethane fraction of Ervatamia coronaria (DFE) leaf extract, identified by LC-MS to contain eight indole-alkaloids as its major constituents. Using 4T1 cell-induced tumour allografts in BALB/c mice, alongside cell-based assays including cell viability, scratch assay, immunoblotting, immunohistochemistry, and scanning electron microscopy, we investigated its mechanisms of action. DFE treatment induced cell cycle arrest in the sub-G1 phase, triggering apoptosis, with little effect on normal cells. Mechanistically, elevated mitochondrial ROS were identified as the primary driver of toxicity, as pre-treatment with NAC reversed DFE’s effects. Additionally, DFE downregulated AKT signalling in breast cancer cells. Importantly, DFE significantly reduced 4T1 tumour growth in vivo, both alone and in combination with doxorubicin, without exerting significant toxicity on healthy mice. These findings support further evaluation of DFE in clinical models.