Inhibition of NF-κB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel

Abstract

Ginsenoside Rg3, the main constituent isolated from Panax ginseng, has been of interest for use as a cancer preventive or therapeutic agent. We investigated here whether Rg3 can inhibit the activity of NF-kappaB, a key transcriptional factor constitutively activated in colon cancer that confers cancer cell resistance to chemotherapeutic agents. To investigate whether RG3 can suppress activation of NF-kappaB, and thus inhibit cancer cell growth, we examined the susceptibility of colon cancer cells (SW620 and HCT116) to treatment with Rg3 (25, 50, 75, 100 microM) and RG3-induced activation of NF-kappaB. RG3 dose-dependently inhibited cancer cell growth through induction of apoptosis and decreased NF-kappaB activity. In a further study of compounds in colon cancer, we used half of the IC(50) dose, values in combined treatments of Rg3 (50 microM) with conventional agents - docetaxel (5 nM), paclitaxel (10 nM) cisplatin (10 microM) and doxorubicin (2 microM). Compared to treatment with Rg3 or chemotherapy alone, combined treatment was more effective (i.e., there were synergistic effects) in the inhibition of cancer cell growth and induction of apoptosis and these effects were accompanied by significant inhibition of NF-kappaB activity. NF-kappaB target gene expression of apoptotic cell death proteins (Bax, caspase-3, caspase-9) was significantly enhanced, but the expression of anti-apoptotic genes and cell proliferation marker genes (Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP), Cox-2, c-Fos, c-Jun and cyclin D1) was significantly inhibited by the combined treatment compared to Rg3 or docetaxel alone. These results indicate that ginsenoside Rg3 inhibits NF-kappaB, and enhances the susceptibility of colon cancer cells to docetaxel and other chemotherapeutics. Thus, ginsenoside Rg3 could be useful as an anti-cancer or adjuvant anti-cancer agent.

Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells

“…We speculate that Rg3 may have antitumor effects in human hepatocellular carcinoma by inhibiting cancer cell growth. This result is consistent with previous studies on the anticarcinogenic effects Rg3 in other malignant tumors (7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Anti-Cancer Effect of the Combination of Thiacremonone and Docetaxel by Inactivation of NF-κB in Human Cancer Cells

“…*p＜0.05 indicates statistically significant differences from the normal group. by 1 or 5 nM of docetaxel in PC-3 and DU145, and then decreased by 10 nM docetaxel as similar to the previous report (Kim et al, 2009). However, the combination of 5 nM docetaxel and 50 μg/ml thiacremonone significantly inhibited the constitutively activated NF-κB DNA binding activity (Fig.…”

“…Our previous data show a concentrationdependent inhibition of cell growth by thiacremonone alone treatment in prostate cancer cells with IC50 values, 210 and 190 μg/ml in PC-3 and DU145 cancer cells after 24 h treatment, respectively (data not shown). Docetaxel treatment for 24 h also inhibited cancer cell growth in a concentration dependent manner with IC 50 values about 12 and 14 nM in PC-3 and DU145 cancer cells, respectiviely (Kim et al, 2009). Subsequent studies were undertaken to examine whether the prostate cancer cells were more sensitive to the cytotoxic effect by the combined regimen of thiacremonone (50 μg/ml, 1/4 dose of IC 50 ) with docetaxel (5 nM, less than half dose of IC 50 value).…”

Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling

“…Several ginsenosides (e.g., Rh2, Rg3, and Rk1) exhibit anti-proliferative and antiangiogenic activities in vitro and in vivo (19)(20)(21). Mechanistically, Rg3 and/or Rh2, Rk1, has been shown to inhibit the NF-κB signaling pathway (22) and cell proliferation, and to induce apoptosis in cancer cell lines (23)(24)(25)(26)(27)(28). Nonetheless, ginsenosides exhibit a broad range of biological activities, including anticancer activities; and their molecular modes of actions may be diverse and remain largely undefined.…”