Selective induction of apoptosis by 7-methyljuglone, its derivatives and isolated compounds from Foeniculum vulgare Mill. on human cancer cells

A naphthoquinone, 7-methyljuglone and some of its 5-hydroxy, 5-acetoxy-, 5-alkoxy- and 1,2,4,5-tetra-O-acetate derivatives were tested for their activity in four human cancer cell lines: breast adenocarcinoma, cervical epithelial carcinoma, oesophageal carcinoma and prostate epithelial carcinoma. Compound 2,5-dihydroxy-7-methyl-1,4-naphthoquinone was found to be the most effective one (exhibited a fifty percent inhibitory concentration (IC50) in the range of 5.3 to 14.7 μM), while the parent compound 7-methyljuglone was less active than several of these derivatives. The IC50 values of 5-hydroxy-6-methyl-1,4-naphthoquinone were found to be between 19.1 and 15.4 μM on the four cell lines. However this compound showed toxicity on peripheral blood mononuclear cells. Six derivatives were selected for mechanistic studies. Considering the findings from cell cycle analysis, caspase 3/7 activation and annexinV-FITC dual labelling, 5-hydroxy-6-methyl-1,4-naphthoquinone was found to have antitumour effect by inducing apoptosis. Two derivatives namely, ‘8-fluoro-5-hydroxy-7- methyl-1,4-naphthoquinone’ and ‘2,5-dihydroxy-7-methyl-1,4-naphthoquinone’ were found to be not toxic on peripheral blood mononuclear cells suggesting their action is specific for tumour cells. Compound 2,5-dihydroxy-7-methyl-1,4-naphthoquinone was found to induce apoptosis through caspase 3/7 activation. In view of the enhanced potencies associated with these derivatives, these analogues may hold considerable therapeutic potential for the treatment of leukaemia cancers. The ethanol extracts of seven plant species (ethnobotanically selected) were also tested for their cytotoxicity, assayed by the XTT assay, against four human cancer cell lines at concentrations ranging from 0.78 to 100 μg/ml. Of all the ethanol extracts, Foeniculum vulgare was found to have the best activity on HeLa cells, which exhibited an IC50 value of 19.97± 0.048 μg/ml. Therefore, it was selected for isolation of the bioactive principles. The extract of Foeniculum vulgare was fractionated using column chromatography with hexane and ethyl acetate at different ratios as eluent. Two known compounds, ‘4-methoxycinnamyl alcohol’ and ‘syringin’ were isolated. The IC50 values of ‘4-methoxycinnamyl alcohol’ and ‘syringin’ were found to be 7.82 ± 0.28 μg/ml and 10.26 ± 0.18 μg/ml respectively on HeLa cells. Both compounds were tested for their cytotoxicity against U937 cells and also on peripheral blood mononuclear cells. At the concentrations of 10 and 100 μg/ml ‘4- methoxycinnamyl alcohol’ showed similar cell proliferation as that of the positive control ‘cisplatin’. ‘Syringin’ however, had much lower cytotoxicity on the U937 cells than ‘4- methoxycinnamyl alcohol’. IC50 was found to be 91.14 ± 0.63 μg/ml. Both ‘syringin’ and ‘4- methoxycinnamyl alcohol’ were not cytotoxic at concentrations of 1 and 10 μg/ml on the PBMCs as compared to cisplatin. ‘4-Methoxycinnamyl alcohol’ was selected based on its activity on the cancer cells, for further investigation with regard to its mechanism of action. On gel electrophoresis it did not show a typical ladder pattern, instead a characteristic smear resulted which indicated necrosis. Two best derivatives of 7-methyljuglone (‘8-fluoro-5-hydroxy-7-methyl-1,4-naphthoquinone’ and ‘2,5-dihydroxy-7-methyl-1,4-naphthoquinone’) and the ethanol extract of F. vulgare warrant further investigation to be considered for their potential as anticancer agents.Dissertation (MSc)--University of Pretoria, 2011.Plant Scienceunrestricte

Criteria for selection and gate reviews of technology innovation projects

This paper describes appropriate project selection criteria and gate review-point criteria for government agencies that fund technology innovation projects in South Africa. Data was gathered via a Delphi survey in which seven expert respondents participated. The most significant project selection criteria and relevant gate reviewing criteria were established. The proposed basic framework consists of fourteen selection criteria, their associated weights, and forty relevant gate reviewing criteria. Commercial risk and feasibility was considered the most important criterion, followed by the team’s skills and competence in second place. The use of these criteria when considering investment in technology innovation projects could improve the likelihood of commercial success.Hierdie artikel beskryf, vir staatsinstansies wat projekte vir tegnologiese innovasie in Suid Afrika befonds, toepaslike kriteria vir die seleksie van projekte en vir oorsig by hersieningspunte aan die einde van projek fases. Data is ingewin deur middel van ʼn Delphi-opname waaraan sewe deskundige respondente deelgeneem het. Die mees beduidende kriteria vir seleksie en oorsig is bepaal. Die voorgestelde raamwerk bestaan uit veertien seleksie-kriteria, relatiewe gewigte vir elk, en veertig kriteria vir hersiening by oorsigpunte. Kommersiële risiko en doenbaarheid word beskou as die belangrikste kriterium, wat gevolg word deur die span se vaardigheid in die tweede plek. Die gebruik van hierdie kriteria wanneer investering in projekte vir tegnologiese innovasie oorweeg word, kan die waarskynlikheid van kommersiële sukses verhoog.At the time this research was conducted, this author was enrolled for the MSc (Project Management) a degree at the Graduate School of Technology Management, University of Pretoria.http://sajie.journals.ac.za/am201

Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum vulgare on selected human cell lines

The present study was carried out to determine the cytotoxic effect of seven plant extracts and the isolated compounds; syringin and 4-methoxycinnamyl alcohol on cancerous and non-cancerous cells. The ethanol extract of F. vulgare was found to exhibit the most significant toxicity with an IC50 value of 19.97 μg/mL on HeLa cells. Bioassay guided fractionation lead to the isolation of two compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed toxicity against MCF-7, HeLa, and DU145 cancer cell line. The results showed that compound 2 showed high toxicity against all the cancer cell lines with IC50 values of 14.24, 7.82 and 22.10 μg/mL, respectively. 4-Methoxycinnamyl alcohol also showed no apoptotic effect in cell cycle analysis after 48 hours at a concentration of 10 μg/mL. However DNA fragmentation study revealed that, necrosis took place at a concentration of 10 μg/mL after 48 h exposure.http://www.tandfonline.com/loi/gnpl202016-09-15hb201

Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines

In an effort to establish new candidates with enhanced anticancer activity of 5-hydroxy-7-methyl-1,4- naphthoquinone scaffold (7-methyljuglone) previously isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone derivatives have been synthesized and assessed for cytotoxicity on selected human cancer lines. These compounds were screened in vitro for anticancer activity on MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8 lM followed by compound (5) with IC50 value of 10.1 and 9.3 lM, respectively. Structure–activity relationship reveals that the fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5 positions played an important role in toxicity.University of Pretoria, South Africa and National Research Foundation (NRF), South Africa.http://www.elsevier.com/locate/bmc2015-09-30hb201

Criteria For Selection And Gate Reviews Of Technology Innovation Projects

This paper describes appropriate project selection criteria and gate review-point criteria for government agencies that fund technology innovation projects in South Africa. Data was gathered via a Delphi survey in which seven expert respondents participated. The most significant project selection criteria and relevant gate reviewing criteria were established. The proposed basic framework consists of fourteen selection criteria, their associated weights, and forty relevant gate reviewing criteria. Commercial risk and feasibility was considered the most important criterion, followed by the teams skills and competence in second place. The use of these criteria when considering investment in technology innovation projects could improve the likelihood of commercial success

Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from <i>Foeniculum vulgare</i> on selected human cell lines

<div><p>This study was carried out to determine the cytotoxic effect of seven plant extracts and the isolated compounds – syringin and 4-methoxycinnamyl alcohol – on cancerous and non-cancerous cells. The ethanol extract of <i>Foeniculum vulgare</i> was found to exhibit the most significant toxicity with an IC₅₀ value of 19.97 μg/mL on HeLa cells. Bioassay-guided fractionation led to the isolation of two compounds, syringin (<b>1</b>) and 4-methoxycinnamyl alcohol (<b>2</b>). Both compounds showed toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that compound <b>2</b> showed high toxicity against all the cancer cell lines with IC₅₀ values of 14.24, 7.82 and 22.10 μg/mL, respectively. 4-Methoxycinnamyl alcohol also showed no apoptotic effect in cell cycle analysis after 48 h at a concentration of 10 μg/mL. However, DNA fragmentation study revealed that necrosis took place at a concentration of 10 μg/mL after 48 h exposure.</p></div