strychnine and Colonic-Neoplasms

Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/β-catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of β-catenin, c-Myc, and p-LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.

Topics: Alkaloids; Animals; Colonic Neoplasms; Humans; Mice; Mice, Nude; Strychnine; Strychnos nux-vomica; Wnt Signaling Pathway

Angiogenesis plays an important role in colon cancer development. This study aimed to demonstrate the effect of brucine on tumour angiogenesis and its mechanism of action. The anti-angiogenic effect was evaluated on the chicken chorioallantoic membrane (CAM) model and tube formation. The mechanism was demonstrated through detecting mRNA and protein expressions of VEGFR2 (KDR), PKCα, PLCγ and Raf1 by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB), as well as expressions of VEGF and PKCβ and mTOR by ELISA and WB. The results showed that brucine significantly reduced angiogenesis of CAM and tube formation, inhibited the VEGF secretion and mTOR expression in LoVo cell and down-regulated the mRNA and phosphorylation protein expressions of KDR, PKCα, PLCγ and Raf1. In addition, the effects of brucine on KDR kinase activity, viability of LoVo cell and gene knockdown cell were detected with the Lance™ assay, WST-1 assay and instantaneous siRNA. Compared to that of normal LoVo cells, the inhibition on proliferation of knockdown cells by brucine decreased significantly. These results suggest that brucine could inhibit angiogenesis and be a useful therapeutic candidate for colon cancer intervention.

Topics: Base Sequence; Cell Division; Cell Line, Tumor; Colonic Neoplasms; DNA Primers; Humans; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Signal Transduction; Strychnine; Vascular Endothelial Growth Factor Receptor-2

In this study, we describe a highly selective etherification procedure of unprotected morroniside catalyzed by molecular iodine in acetone. The etherification reaction furnished 7-O-alkyl ether derivatives in reasonable yields within few hours under neutral conditions. Studies of the obtained products on cytotoxicity activity in colon 26-L5 cell line were examined. Among the tested compounds, 7-O-dodecylmorroniside showed moderate cytotoxic activity, having IC50 values equal to 20.9 microM.

Topics: Acetone; Animals; Antineoplastic Agents, Phytogenic; Catalysis; Cell Line, Tumor; Colonic Neoplasms; Ethers; Glycosides; Iodine; Mice; Molecular Structure; Plant Roots; Strychnos

Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, a well known African shrub or little tree. The roots contain quaternary alkaloids, which are used to make a curare-like arrow poison. However, tertiary alkaloids isolated from the same plant possess cytotoxic activities against mammalian cells and protozoa. The effect of ISP has been investigated on the growth and viability of HCT-116 colon cancer cells during their exponentially growing phase. ISP induced apoptotic cell death as shown by the translocation of phosphatidylserine from the inner layer to the outer layer of the plasma membrane, chromatin condensation, DNA fragmentation, and caspase-3 and -9 activation. ISP provoked also cell cycle arrest in the G(2)-M phase. We also showed that the expression of p53 was not modified in ISP-treated cells, but that p21 was induced in a p53-independent manner. Finally, we demonstrated that ISP did not affect the catalytic activity of human topoisomerases I and II. In conclusion, ISP, which promotes cell death by a p53-independent apoptotic pathway, could be an interesting lead for cancer chemotherapy.

Topics: Alkaloids; Antineoplastic Agents; Apoptosis; Carbolines; Caspase 8; Caspase 9; Caspases; Cell Cycle; Colonic Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cytochrome c Group; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Humans; Strychnos; Tumor Cells, Cultured; Tumor Suppressor Protein p53