aconitine and Liver-Neoplasms

Aconitine, the main component in Radix Aconiti Lateralis Preparata, not only exerts the anti-tumor effect on Hepatocellular Carcinoma (HCC) but also damages on immune system. In the present study, Crude Monkshood Polysaccharide (CMP), another one natural composition component originated from the same herbal with aconitine, combined with aconitine to investigate the effects on HCC and immunity in vitro and in vivo. The combination of CMP and aconitine enhanced the ability of the immunocyte to kill the tumor cell in vitro and had an additive effect on anti-HCC in vivo. Aconitine-CMP in combination improved the spleen weights, spleen index, thymus weights, thymus index. Elevated CD4

Topics: Aconitine; Aconitum; Adjuvants, Immunologic; Animals; Carcinoma, Hepatocellular; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Proliferation; In Vitro Techniques; Interferon-gamma; Interleukin-6; Liver Neoplasms; Lymphocytes; Macrophages; Mice; Neoplasm Transplantation; Organ Size; Plant Extracts; Polysaccharides; Spleen; Thymus Gland; Tumor Necrosis Factor-alpha

Hepatocellular carcinoma (HCC) is the third leading cause of tumor-related deaths in the word. Lappaconitine (LA), a diterpenoid alkaloid, exerts antitumor activities. However, the effects and mechanisms of LA sulfate (LS) on HCC remain unclear. This study evaluated the activities and explored the underlying mechanisms of LS in HCC cell line HepG2 cells.. The cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assay, respectively. The cell cycle distribution was detected by propidium iodide (PI) staining assay. The apoptosis was detected by Annexin -V-fluorescein isothiocyanate (FITC)/PI double staining assay. The cell cycle arrest and apoptosis-related proteins were estimated by western blot analysis. The mitochondrial membrane potential (MMP) was -determined through the 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimi-dazolyl carbocyanine iodide (JC-1) staining assay. The reactive oxygen species (ROS) was monitored by 20-70-dichlorofluorescein diacetate (DCFH-DA) staining assay. In vivo antitumor activities were investigated by HepG2 xenograft model.. Our results showed that LS significantly -inhibited the viability and proliferation of HepG2 cells. LS triggered G0/G1 cell cycle arrest, apoptosis and caspase activation. Furthermore, LS induced MMP loss and ROS accumulation. Additionally, LS suppressed the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) signaling pathway. An in vivo assay showed that LS exhibited a pronounced antitumor effect in nude mice bearing HepG2 xenografts.. Our results demonstrated that LS is a promising therapeutic agent for HCC directed -toward the proliferation inhibition and the induction of apoptosis.

Topics: Aconitine; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle Checkpoints; Cell Proliferation; Glycogen Synthase Kinase 3 beta; Hep G2 Cells; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Mice; Mice, Nude; Mitochondria, Liver; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction

To investigate the anticancer activity of a chinese medical mixture, WRCP (warming and relieving Cold Phlegm), on hepatocarcinoma Bel-7402 cells.. Fingerprints of WRCP, which were composed of aqueous extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng and Gekko swinhonis Guenther, and aconitine, which could be isolated from Aconitum carmichaeli and have the potential toxicity, were identified by high pressure liquid chromatography. Bel-7402 cells were grown in the presence of WRCP, As(2)O(3) or all-trans-retinoic acid (ATRA). Cell proliferation and viability were determined by trypan blue stain. Apoptosis and cell cycle of Bel-7402 cells were detected by flow cytometry. Morphologic and ultrastructural variations were determined under optic and electronic microscopy. The secretion of alpha-fetoprotein and albumin was detected by radioimmunoassay.. The average quality of aconitine is 1.15 +/- 0.10 microg per 7.5 g extracts. WRCP could suppress the proliferation and viability of Bel-7402 cells. The percentage of apoptosis cells and S phase cells increased on WRCP-treated cells. Treated with WRCP, Bel-7402 cells showed ultrastructural features of differentiation. The alpha-fetoprotein secretion decreased while the albumin secretion increased (P < 0.001, P < 0.001, respectively) markedly in WRCP-treated cells.. WRCP can affect the proliferation, differentiation and apoptosis of Bel-7402 cells. It can arrest cells in S phase and has strong cytotoxicity to Bel-7402 cells.

Topics: Aconitine; Aconitum; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drugs, Chinese Herbal; Humans; Liver Neoplasms; Lizards; Panax notoginseng; Phytolacca; Tissue Extracts