Biomedical application of silver nanoparticles (AgNPs) has been rapidly increasing. Owing to their strong antimicrobial activity, AgNPs are used in dermatology in the treatment of wounds and burns. However, recent evidence for their cytotoxicity gives rise to safety concerns. This study was undertaken as a part of an ongoing programme in our laboratory to develop a topical agent for wound healing. Here, we investigated the potential toxicity of AgNPs using normal human dermal fibroblasts (NHDF) and normal human epidermal keratinocytes (NHEK) with the aim of comparing the effects of AgNPs and ionic silver (Ag-I). Besides the effect of AgNPs and Ag-I on cell viability, the inflammatory response and DNA damage in AgNPs and Ag-I–treated cells were examined. The results showed that Ag-I were significantly more toxic than AgNPs both on NHDF and NHEK. Non-cytotoxic concentrations of AgNPs and Ag-I did not induce DNA strand breaks and did not affect inflammatory markers, except for a transient increase in interleukin 6 levels in Ag-I–treated NHDF. The results showed that AgNPs are more suitable for the intended application as a topical agent for wound healing up to the concentration 25 µg/mL.

Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug.

Modern research has shown that Amaryllidaceae alkaloids represent a rich reservoir of potential small chemical molecules exhibiting several medicinal properties through various mechanisms. Among the many Amaryllidaceae compounds, galanthamine has been given a great amount of attention due to the fact that it possesses potent acetylcholinesterase inhibitory activity. In spite of the amount of evidence indicating the potential usefulness of Amaryllidaceae alkaloids in therapy, research groups have focused their attention on the other alkaloids present in this plant family. New investigations have shed light on many aspects of the structure of Amaryllidaceae alkaloids and on their semisynthetic modification, function, and mechanisms underlying in vitro and in vivo activity. In addition, Amaryllidaceae alkaloids have frequently been identified as having promising cytotoxic properties against cancer cell lines. While followup studies have repeatedly shown that Amaryllidaceae alkaloids and their derivatives demonstrate antiproliferative, cytotoxic and apoptosis-inducing activity, the mechanisms remain unclear. This review addresses the most important Amaryllidaceae alkaloids with anticancer potential, particularly those that have been studied for the purpose of gaining a better understanding of the basis of the activity at the cellular and molecular level.

This study focuses on the comparative in vitro cytotoxicity of chelidonine and homochelidonine on human cancer and non-cancer cells. Both alkaloids produced a decrease in cellular growth in a dose-dependent manner exhibiting greater potency in cancer cells. The growth inhibitory effect was evidenced in both ovarian carcinoma A2780 and lung fibroblast MRC-5 cells by inducing G2 and mitotic phase cell cycle arrest. Results indicated that the extent of apoptosis induced by chelidonine and homochelidonine was correlated to sensitivity to the antiproliferative activity of the evaluated compounds. Western blotting suggested that the cellular toxicological mechanism of chelidonine is related to the differential upregulation of phospho-Chk2, p21 Cip1/Waf1 , phospho-ERK1/2 and phospho-p38 in various cell types, leading to alternations in the suppression of proliferation and either induction or prevention of apoptosis. Chelidonine showed the more potent effects and also affected the cell cycle checkpoints and MAPK signaling pathways within cells.

Forty-six isoquinoline alkaloids, of eleven structural types isolated in our laboratory, have been evaluated for their cytotoxicity against two cancer cell lines (Caco-2 and Hep-G2 cancer cells), as well as against normal human lung fibroblast cells. Only scoulerine, aromoline, berbamine and parfumidine showed significant cytotoxic effects, but only scoulerine was active against both Caco-2 and Hep-G2 cells (IC 50 values 6.44 + 0.87 and 4.57 + 0.42, respectively). Unfortunately, except for parfumidine, the other active alkaloids were also cytotoxic to the normal human lung fibroblast cells.