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The intrinsic, or mitochondrial, pathway is activated by honeys polyphenolic components that cause mitochondrial membrane depolarization and activate caspases 3, 7, and 9 ( In vivo studies using Wistar rats in which honey was ingested with Aloe vera showed that these apoptotic effects complement the cell cycle arrest described in Section 4.1 ( The extrinsic, or death receptor-mediated, pathway is also controlled by honey, particularly through its effect on epithelialmesenchymal transition (EMT)a key component in tumor invasion and metastasis ( in vitro , with some clinical trials still needed to fine tune dosing and therapeutic effects