The Synergistic Apoptotic Interaction of Panaxadiol and Epigallocatechin Gallate in Human Colorectal Cancer Cells

Colorectal cancer is the third most common malignancy in the United States and the second most frequent cause of cancer-related death (HawkLevin, 2005; Jemal et al., 2010). Although curative surgical resection is possible in 70–80% of patients after diagnosis, almost half of them will die from recurrence of cancer (Yao et al., 2008). However, natural products have been a valuable source of new candidate compounds for adjuvant therapy (Cragg et al., 2009; Gullett et al., 2010). We recently observed that a ginsenoside aglycon protopanaxadiol (PPD) showed antiproliferative effects on human colorectal cancer cells (Du et al., 2011). Panaxadiol (PD), a pseudoaglycone of diol-type triterpenoid with a dammarane skeleton (Fig. 1), is an active anticancer compound in steamed American ginseng (Qi et al., 2010). We also showed that steamed American ginseng extract increased reactive oxygen species (ROS) levels and induced mitochondrial damage in colorectal cancer cells (Li et al., 2010; Wang et al., 2009). We hypothesize that antioxidants may decrease the level of ROS and enhance PD-induced apoptosis in colorectal cancer cells, and this hypothesis was proven in part by our recent observation that the tumoricidal effect of PD was enhanced by a natural phenol compound epicatechin (Rodriguez et al., 2010). Fig. 1 Chemical structures of panaxadiol (PD) and epigallocatechin gallate (EGCG). Epigallocatechin gallate (EGCG), a well-known antioxidant, is believed to be the major biologically active compound in green tea (Kawai et al., 2005; Kim et al., 2009; Nakazato et al., 2005). A highly popular beverage globally, green tea contains a number of polyphenol compounds referred to as catechins, which have been demonstrated to possess strong ROS scavenging activity. Of these, EGCG showed the most potent antioxidant potential (LambertElias, 2010). In this study, we investigated the possible synergistic antiproliferative effects of PD and EGCG in two human colorectal cancer cell lines, HCT-116 and SW-480. The effects of these compounds on cell cycle and apoptosis were also evaluated, and the docking model of these compounds to annexin V, a protein related to apoptosis, was simulated.