sapogenins and Stomach-Neoplasms

20(S)-protopanaxadiol (PPD), a metabolite of

Topics: Apoptosis; Autophagy; Cell Line, Tumor; Ginsenosides; Humans; Panax; Sapogenins; Stomach Neoplasms

Cycloastragenol (CAG), a triterpene aglycone is commonly prescribed for treating hypertension, cardiovascular disease, diabetic nephropathy, viral hepatitis, and various inflammatory-linked diseases.. We investigated CAG for its action on signal transducer and activator of transcription 3 (STAT3) activation cascades, and its potential to sensitize gastric cancer cells to paclitaxel-induced apoptosis.. The effect of CAG on STAT3 phosphorylation and other hallmarks of cancer was deciphered using diverse assays in both SNU-1 and SNU-16 cells.. We observed that CAG exhibited cytotoxic activity against SNU-1 and SNU-16 cells to a greater extent as compared to normal GES-1 cells. CAG predominantly caused negative regulation of STAT3 phosphorylation at tyrosine 705 through the abrogation of Src and Janus-activated kinases (JAK1/2) activation. We noted that CAG impaired translocation of STAT3 protein as well as its DNA binding activity. It further decreased cellular proliferation and mediated its anticancer effects predominantly by causing substantial apoptosis rather than autophagy. In addition, CAG potentiated paclitaxel-induced anti-oncogenic effects in gastric tumor cells.. Our results indicate that CAG can function to impede STAT3 activation in human gastric tumor cells and therefore it may be a suitable candidate agent for therapy of gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Janus Kinase 1; Janus Kinase 2; Paclitaxel; Phosphorylation; Phytotherapy; Sapogenins; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms

25-Hydroxyprotopanaxadiol (25-OH-PPD) and 25-methoxylprotopanaxadiol (25-OCH3-PPD), two ginseng sapogenins, have potent antitumor activity and their effects on gastric cancer (BGC-823, SGC-7901, MKN-28) cells and a gastric mucosa (GES-1) cell line are reported.. Both compounds significantly inhibited the growth of gastric cancer cells, while having lesser inhibitory effects on GES-1 cells by MTT assay. A mechanistic study revealed that the two ginseng sapogenins could induce apoptosis in BGC-823 cells by morphological observation, DNA fragmentation, flow cytometry and western blot analysis. Besides, the apoptosis was inhibited by Ac-DEVD-CHO, a caspase 3 inhibitor, which was confirmed by cell viability analysis.. These results indicate that 25-OH-PPD and 25-OCH3-PPD have potential to be promising agents for the treatment of gastric cancer.

Topics: Antineoplastic Agents; Caspases; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA Damage; Ginsenosides; Humans; Panax; Sapogenins; Signal Transduction; Stomach Neoplasms

Seven new compounds, including three new flavans [tupichinol A-C (1-3)], three new spirostanol sapogenins [tupichigenin D-F (4-6)], and one new pregnane genin [tupipregnenolone (7)], together with 18 known compounds, were isolated from the underground parts of Tupistra chinensis. The structures of the new compounds were elucidated by spectroscopic analysis and chemical evidence. The structures and relative stereochemistry of 1 and 9 were further confirmed by single-crystal X-ray crystallographic analysis. Compounds Delta(25(27))-pentrogenin, 10, and ranmogenin A showed 100%, 96%, and 80% inhibition, respectively, against human gastric tumor (NUGC) cells at a concentration of 50 microM. Delta(25(27))-pentrogenin showed 100% inhibition against human nasopharyngeal carcinoma (HONE-1) cells at a concentration of 50 microM.

Topics: Antineoplastic Agents, Phytogenic; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Flavonoids; Humans; Liliaceae; Molecular Conformation; Molecular Structure; Nasopharyngeal Neoplasms; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Pregnanes; Sapogenins; Stereoisomerism; Stomach Neoplasms; Taiwan; Tumor Cells, Cultured