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They tend to upregulate the pro-apoptotic protein Bax and inhibit the anti-apoptotic protein Bcl-2, altering the Bax/Bcl-2 ratio to promote the release of cytochrome c, which in turn activates downstream apoptosis-executing proteins such as caspase-3 and caspase-9 ( 3.1.3 Inhibition of tumor microenvironment and angiogenesis Polyphenols also exert anticancer effects by remodeling the tumor microenvironment