, 2010). Dasatinib exhibited a synergistic effect with trastuzumab on inducing apoptosis and DNA damage without caspase activation but with a decrease in the levels of procaspases. The caspase-3-independent mode of action of CHO10 against SK-BR-3 cells may require further study to be elucidated clearly. When HER2/HER3 signaling is decreased, which reduces Akt signaling, TAM-resistance in ER-positive breast cancer cells is reduced (Lindberg et al., 2011 and Ghayad et al., 2010). HER2 overexpression is one of the primary mechanisms underlying the acquisition of TAM resistance

(Ring and Dowsett, 2004, Bunone et al., 1996, Benz et al., 1993 and Chung et al., 2002). Therefore, CHO10 was evaluated for its ability to reverse TAM resistance in selleckchem BT474 cells. A combination of CHO10 (1 μM) and TAM enhanced the growth inhibition of BT474 cells from 16.1% to 84.3% with a 5 μM TAM treatment (Fig. 4). This result is consistent with the observation that the reduction of PAX2, which is required for the active repression of HER2 in breast cancer, caused HER2-driven TAM-resistant cell growth by using PAX2 siRNA (Hurtado et al., 2008). A novel inhibitor that reduces HER2 expression and signaling was also evaluated for the inhibition of TAM-resistant breast cancer cell growth; chenodeoxycholic acid treatment reduced HER2 expression and p42/44 MAPK phosphorylation in TAM-resistant breast cancer cells Metformin via the inhibition of binding

of the nuclear factor-κB transcription factor with the HER2 promoter (Giordano et al., 2011). Roscovitine, a 2,6,9-substituted purine analog, known as a selective orally bioavailable CDK2 inhibitor, attenuated HER2 expression and ameliorated the MCF-7 HER2-deriven TAM-resistant xenograft tumor (Meijer et al., 1997 and Nair et al., 2011). The anti-tumor activity of CHO10 was confirmed by a study with xenografted

mice; treatment with these 1 mg/kg five times every 2 days significantly reduced HER2-positive NCI-H460 or DLD-1 cells subcutaneously implanted xenograft tumors (Fig. 5) (Bunn et al., 2001 and LaBonte et al., 2011). In conclusion, our data provide insight into the design of small molecules that induce HER2 down-regulation by interfering with the ESX–Sur2 interaction. Our study also afforded a rationale for a strategy of combined endocrine therapy with a novel ESX–Sur2 interaction inhibitor, which is capable of reducing HER2 expression and signaling, thereby inhibiting HER2-driven TAM-resistant cancer cell growth. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0071926, 2009-0066925, 2010-0002646). “
“Studies have underscored the anticancer and/or antitumor activities of 3,3′-diindolylmethane (DIM), a metabolite of the naturally-occurring indole-3-carbinol (I3C) found in cruciferous vegetables such as broccoli (Chen et al., 2012 and Shorey et al.