Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.

Two natural ent-kaurene diterpenoids, ent-15α-angeloyloxykaur-16-en-3β-ol (7) and ent-15α-angeloyloxykaur-16-en-3β,9-diol (8), were extracted from the aerial parts of Distichoselinum tenuifolium, and six new derivatives were synthesised from compound (7). The antitumour properties of these natural and derivative ent-kaurenes (2, 7, 9–13) were evaluated in three cancer cell lines: HT29 (colon cancer), HepG2 (hepatocellular carcinoma), and B16-F10 (murine melanoma). Among them, the synthesised ent-kaurene (13) containing an exomethylene–cyclopentanone moiety showed the strongest antiproliferative effects in all cell lines tested, with significantly lower IC50 values around 2.5 μM. Compounds 13 and 12, together with their precursor (7), were selected for further comparative cytometric and microscopic analyses. Cell cycle studies revealed that derivatives 12 and 13 exhibited promising cytostatic activity by inducing selective G2/M phase arrest, particularly effective in HT29 and HepG2 cells. Conversely, precursor (7) showed no significant effect on B16-F10 cell cycle distribution. The Annexin V-FITC/PI double staining assay confirmed the robust apoptotic effects of compounds (7), 12 and 13, with compound 13 inducing up to 99% total apoptosis and exhibiting significant apoptotic activity in all cell lines tested. These apoptotic effects were closely linked to mitochondrial dysfunction, as evidenced by a marked loss of mitochondrial membrane potential and reduced Rh123 fluorescence in treated cells, thereby activating the intrinsic apoptotic pathway. These findings highlight the critical role of mitochondrial disruption in the cytotoxic mechanisms of these ent-kaurenes and underscore their potential as promising anticancer agents.