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The article discusses research which evaluated the amaryllidaceae alkaloid from Lycoris radiata or red spider lily, a bulbous perennial plant known as a botanical source of medicine, galantamine. Topics discussed include the isoquinoline-based amine components which possessed various pharmacological activities and inhibitory effect of amaryllidaceae alkaloids on acetylcholinesterase.

Cancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor-specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose-deprived conditions. Here we identify arctigenin (ARC-G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC-G blocked expression of UPR target genes such as phosphorylated-PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2α during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase-9 and -3. Furthermore, ARC-G suppressed tumor growth of colon cancer HT-29 xenografts. Our results demonstrate that ARC-G can be served as a novel type of antitumor agent targeting the UPR in glucose-deprived solid tumors. J. Cell. Physiol. 224:33–40, 2010 © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Glucose deprivation, a pathophysiological cell condition, causes up-regulation of GRP78 and induction of etoposide resistance in human cancer cells. The induction of drug resistance can be partly explained by the fact that GRP78 can block activation of caspase-7 induced by treatment with etoposide. Therefore, downregulating GRP78 expression may be a novel strategy anticancer drug development. Based on that premise, we established a screening program for anticancer agents that exhibit preferential cytotoxic activity for etoposide-resistant cancer cells under glucose-deprived conditions. We recently isolated an active compound, AR-054, from the culture broth of Streptomyces sp., which prevents stress-induced etoposide resistance in vitro. AR-054 was identified as piericidin A, a prototypical compound, by ESI-MS analysis and various NMR spectroscopic methods. Here, we showed that piericidin A suppressed the accumulation of GRP78 protein and was also highly toxic to etoposide-resistant HT-29 cells, with IC50 values for colony formation of 6.4 and 7.7 nM under 2-deoxyglucose supplemented and glucose-deprived conditions, respectively. Interestingly, piericidin A had no effect under normal growth conditions. Therefore, we suggest that piericidin A prevents up-regulation of GRP78, and exhibits cytotoxicity in glucose-deprived HT-29 cells that are resistant to etoposide. J. Cell. Physiol. 215: 243–250, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Natural marine products have recently become the focus of increased research interest, due to their potential pharmacological activities. Therefore, we have screened 50 varieties of marine seaweed and determined that the methanolic extracts from Plocamium telfairiae(PTE) exhibited a cytotoxic effect against HT-29 human colon carcinoma cells. In this study, we report on the cytotoxic activity and mechanism of PTE-induced apoptosis in HT-29 cells. The treatment of HT-29 cells with various PTE concentrations resulted in the inhibition of growth and the induction of apoptosis in a dose-dependent manner, as determined by the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, a lactate dehydrogenase release assay, a morphological assay, and a colony formation assay. Interestingly, we also detected apoptotic bodies on Hoechst staining and attempted to determine whether the PTE-induced apoptosis involved the caspase pathway, using a caspase colorimetric assay. The activation of caspases-8, -9, -3, and -7 and the specific proteolytic cleavage of poly(ADP-ribose) polymerase were detected over the course of apoptosis induction. Our results showed that PTE may function as a chemopreventive andor chemotherapeutic agent in colon carcinoma cells via the reduction of cell viability and the induction of apoptosis. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common cause of cancer-related deaths in the world. Surgical intervention followed by chemotherapy remains the primary approach to treatment since colon cancers remain refractory to most chemotherapeutic agents. Based on that, we established a program to screen natural products for cytotoxic activity, employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay system utilizing HT-29 human colon cancer cells. During the course of our screening, we found that the methanolic extract of silkworm droppings (SDME) has cytotoxic effects on HT-29 cells. In the present study, we investigated the possible mechanisms by which SDME exerts its antiproliferative activity in HT-29 cells. As expected, SDME inhibited growth of HT-29 cells in a dose-dependent manner as assessed by the MTT reduction assay, the lactate dehydrogenase release assay, and the colony formation assay. We also investigated whether the apoptotic effects induced by SDME involve the caspase pathway using the caspase colorimetric assay. Interestingly, caspase-9 and -3, but not caspase-8, were activated in response to SDME treatment. Taken together, these results clearly indicate that the induction of apoptosis by SDME involves a mitochondrial-mediated pathway and strongly suggest that SDME may potentially be a chemotherapeutic agent for human colon cancer. [ABSTRACT FROM AUTHOR]