Fig. 7

Hypothetical overview of multiple actions of β-escin on cancer stem-like features, HER2/HER3/Akt pathway and trastuzumab resistance within HER2-positive breast cancer. β-escin exerts antitumor activity via the intrinsic mitochondrial apoptotic pathway and suppression of cancer stem-like properties including CD44^high/CD24^low stem-like population and ALDH1 activity. Mitochondrial-mediated apoptosis was accompanied by elevated oxidative stress and a marked increase in active p18Bax fragment levels, leading to the release of cytochrome c as well as consequent activation of caspase-3 and caspase-7. β-escin impairs the HER2/HER3/Akt pathway coinciding with downregulation of truncated-p95HER2 in HER2-positive breast cancer cells that are both trastuzumab-sensitive and –resistant