Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human colorectal cancer cells

Abstract

Objectives Panaxadiol (PD) is a purified sapogenin of ginseng saponins that exhibits anticancer activity. Irinotecan (IRN) is a second line anticancer drug, but clinical treatment with IRN is limited due to side effects. In this study, we investigated the possible synergistic anticancer effects of PD and IRN on human colorectal cancer cells and explored the potential role of apoptosis in the synergistic activities. Key findings The combination of PD and IRN significantly enhanced antiproliferative effects in HCT-116 cells (P < 0.05). Cell cycle analysis demonstrated that combining IRN treatment with PD significantly increased the G1-phase fractions of cells, compared with IRN treatment alone. In apoptotic assays, the combination of PD and IRN significantly increased the percentage of apoptotic cells compared with IRN alone (P < 0.01). Increased caspase 3 and caspase 9 activities were observed after treating with PD and IRN. The synergistic apoptotic effects were also supported by docking analysis, which demonstrated that PD and IRN bound two different chains of the caspase 3 protein. Conclusions Data from this study suggested that caspase 3- and caspase 9-mediated apoptosis may play an important role in the PD enhanced antiproliferative effects of IRN on human colorectal cancer cells.

Phytochemistry, pharmacology, and clinical use of Panax notoginseng flowers buds

“…In recent decades, natural products and their derivatives including paclitaxel (Khanna, Rosenberg, & Vail, ) and matrines (Yong, Wu, & Lu, ) with high anticancer bioactivity have been developed into anticancer agents for clinical use. Panaxadiols are the principal components of total saponins of FBP, and some reports have demonstrated their important role in enhancing antiproliferative effects and apoptotic induction during the treatment of human colorectal cancer cells with irinotecan and 5‐fluorouracil (Du et al, ; Li et al, ). In addition, some studies have demonstrated anticancer activities of FBP.…”

Exogenous Morphine Inhibits Human Gastric Cancer MGC-803 Cell Growth by Cell Cycle Arrest and Apoptosis Induction

“…The process of apoptosis is regulated by several proteins that either inhibit or promote apoptotic cell death. Caspase-9 and caspase-3, members of the cysteine protease family, are considered to be the central proteins in the execution of apoptosis (Bhardwaj et al, 2003;Du et al, 2012) while survivin is a identified member of the inhibitor of apoptosis protein family (Idenoue et al, 2005). Suzuki and Shiraki (2001) reported that survivin plays an important role in the suppression of apoptosis by either directly or indirectly inhibiting the activity of caspases.…”

Herbal Medicines as Adjuvants for Cancer Therapeutics

“…Increased caspase 3 and caspase 9 activities were observed after treatment with both compounds, suggesting that the apoptosis was caspase-related cell death. The synergistic apoptotic effects were also supported by docking analysis, which demonstrated that panaxadiol and irinotecan bound two different chains of the caspase 3 protein (Du et al , 2012). …”

“…Because the combined use of irinotecan and panaxadiol significantly upregulated the expression of caspase 3, the Surflex-Dock program was used to determine the binding sites of panaxadiol and irinotecan to caspase 3. The binding affinities of test compounds to different binding sites were also determined, along with the locations of the hydrogen bonds formed (Du et al , 2012). …”