ginsenoside-rg3 and Colonic-Neoplasms

Invasion and metastasis are the major causes leading to the high mortality of colon cancer. Ginsenoside Rg3 (Rg3), as a bioactive ginseng compound, is suggested to possess antimetastasis effects in colon cancer. However, the underlying molecular mechanisms remain unclear. In this study, we reported that Rg3 could effectively inhibit colon cancer cell invasion and metastasis through

Topics: Animals; Antineoplastic Agents; Colonic Neoplasms; Down-Regulation; Epithelial-Mesenchymal Transition; Ginsenosides; Humans; Interleukin-6; Male; Mice, Inbred BALB C; Neoplasm Metastasis; Receptors, Notch; Signal Transduction; Transcription Factor HES-1; Tumor Cells, Cultured

Chemotherapy is one of the most commonly used treatments for patients with advanced colon cancer, yet the toxicity of chemotherapy agents, such as 5‑fluorouracil (5‑FU), limits the effectiveness of chemotherapy. Ginsenoside Rg3 (Rg3) is an active ingredient isolated from ginseng. Rg3 has been shown to display anticancer effects on a variety of malignancies. Yet, whether Rg3 synergizes the effect of 5‑FU to inhibit the growth of human colon cancer remains unknown. The present study was designed to ascertain whether Rg3 is able to enhance the anti‑colon cancer effect of 5‑FU. The results revealed that combined treatment of Rg3 and 5‑FU significantly enhanced the inhibition of the proliferation, colony formation, invasion and migration of human colon cancer cells (SW620 and LOVO) in vitro. We also found that combined treatment of Rg3 and 5‑FU significantly enhanced the apoptosis of colon cancer cells by activating the Apaf1/caspase 9/caspase 3 pathway and arrested the cell cycle of the colon cancer cells in G0/G1 by promoting the expression of Cyclin D1, CDK2 and CDK4. In addition, the PI3K/AKT signaling pathway in colon cancer cells was suppressed by Rg3 and 5‑FU. In vivo, Rg3 synergized the effect of 5‑FU to inhibit the growth of human colon cancer xenografts in nude mice. Similarly, combined treatment of Rg3 and 5‑FU altered the expression of colon cancer protein in vivo and in vitro. Collectively, the present study demonstrated that ginsenoside Rg3 enhances the anticancer effect of 5‑FU in colon cancer cells via the PI3K/AKT pathway.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Drug Synergism; Fluorouracil; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Xenograft Model Antitumor Assays

Colorectal cancer (CRC) is a major malignancy characterized by a high metastasis rate. Systematic chemotherapy is important for patients with advanced CRC. However, many limitations (e.g., side effects to normal organs, shorter circulation time, and unsatisfactory tumor inhibition results) of traditional chemotherapy restrict its further application. Thus, it is necessary to find a method to overcome these challenges and improve the efficacy of CRC treatment. In this study, 20(S)-ginsenoside (Rg3) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) (mPEG-b-P(Glu-co-Phe)) nanoparticles (Rg3-NPs) were prepared. mPEG-b-P(Glu-co-Phe)-based drug delivery systems are pH sensitive that can target cancer cells and circulate for longer in blood. Rg3 could be released rapidly from the nanoparticles within tumor cells. A subcutaneous colon cancer mouse model was developed to evaluate the anticancer efficiency of the Rg3-NPs. The in vivo study indicated that the Rg3-NPs could significantly inhibit tumor proliferation by decreasing the expressions of proliferating cell nuclear antigen, resulting in tumor apoptosis through the increased expressions of caspase-3. Our study demonstrated the marked potential of the Rg3-NPs to treat CRC.

Topics: Animals; Cell Line, Tumor; Colonic Neoplasms; Drug Delivery Systems; Ginsenosides; Humans; Male; Mice, Nude; Nanoparticles; Peptides; Polyethylene Glycols; Polyglutamic Acid; Xenograft Model Antitumor Assays

To study the mechanism of the inhibitory effect of ginsenoside Rg3 on colon cancer cell migration.. Transwell migration assays were performed to investigate the inhibitory effect of ginsenoside Rg3 on SW480 cell migration. Electrophoretic mobility shift assays (EMSAs) and dual luciferase reporter assays were used to study the suppression capability of Rg3 on nuclear factor kappa B (NF-κB) activity. Western blotting was adopted to determine protein levels.. Two-hundred micromolar ginsenoside Rg3 significantly inhibited SW480 cell migration (P < 0.05). EMSA showed that Rg3 suppressed the DNA binding ability of NF-κB. Dual luciferase reporter assay showed that Rg3 decreased NF-κB-regulated gene transcription (P < 0.01). Western blots indicated that Rg3 down-regulated expression of the NF-κB-regulated matrix metalloproteinase 9, cyclooxygenase-2 and C-Myc. An NF-κB inhibitor, pyrrolidine dithiocarbamate, enhanced the inhibitory effect of Rg3 on SW480 cell migration.. Ginsenoside Rg3 has a strong antitumor migration capability by suppressing NF-κB activity and expression of NF-κB-regulated gene products. It could be a good adjuvant for colon cancer patients during the course of chemotherapy.

Topics: Apoptosis; Cell Movement; Colonic Neoplasms; Down-Regulation; Ginsenosides; Humans; NF-kappa B

Ginseng is a well known herbal medicine in Asia, and ginsenoside Rg3 has anti-cancer and various pharmacological effects. In particular, 20S-ginsenoside Rg3 may increase the anti-proliferative effects of chemotherapy. The authors investigated the mechanism of the anti-proliferative effect of 20S-Rg3 at the protein level in HT29 colon cancer cells. MTT, caspase-3 assays, and flow cytometry analysis were performed to determine cytotoxicity and apoptosis, and proteomic analysis was performed by two-dimensional gel electrophoresis and MALDI-TOF/TOF MS, and a database was used to identify protein changes in 20S-Rg3 treated HT29 cells. The proteins identified included down-regulated Rho GDP dissociation inhibitor, up-regulated tropomyosin1, and annexin5 and glutathione s-transferase p1, which are apoptosis associated proteins. The anti-proliferative mechanism of 20S-Rg3 was found to be involved in mitotic inhibition, DNA replication, and repair and growth factor signaling. The findings of this study suggest that the cytotoxicity of 20S-Rg3 in colon cancer is dependent on several mechanisms, including apoptosis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Electrophoresis, Gel, Two-Dimensional; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Proteins; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stereoisomerism

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.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Cell Cycle Proteins; Cell Proliferation; Cisplatin; Colonic Neoplasms; Docetaxel; Dose-Response Relationship, Drug; Doxorubicin; Ginsenosides; HCT116 Cells; Humans; Inhibitory Concentration 50; NF-kappa B; Paclitaxel; Taxoids