Design and Synthesis of Novel Dehydroepiandrosterone Analogues as Potent Antiproliferative Agents

The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hela, HepG-2, BEL7402, MCF-7, and HCT116. Several of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound was (E)-3-hydroxy-16-((1-(4-iodophenyl)-1H-1,2,3-triazole-4-yl)methylene)-10,13-dimet-hyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14)-one (compound 2n), which showed considerably high antiproliferative activity in the HepG-2 cell line, with an IC50 value of 9.10 µM, and considerably high activity against the MCF-7 cell line, with an IC50 value of 9.18 µM. Flow cytometry assays demonstrated that compound 2n exerted antiproliferative effects by arresting cells in the G2 phase of the cell cycle and inducing apoptosis.

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Antioxidants, Phytochemicals, and Cytotoxicity Studies onPhaleria macrocarpa(Scheff.) Boerl Seeds

BioMed Research International ◽

10.1155/2014/410184 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Ma Ma Lay ◽

Saiful Anuar Karsani ◽

Behrooz Banisalam ◽

Sadegh Mohajer ◽

Sri Nurestri Abd Malek

Keyword(s):

Human Cancer ◽

Cytotoxic Effects ◽

Nutritional Values ◽

Water Fraction ◽

Human Cancer Cells ◽

Fiber Protein ◽

Cytotoxicity Studies ◽

Normal Human ◽

Lung Cell Line ◽

Mcf 7

In recent years, the utilization of certain medicinal plants as therapeutic agents has drastically increased.Phaleria macrocarpa(Scheff.) Boerl is frequently used in traditional medicine. The present investigation was undertaken with the purpose of developing pharmacopoeial standards for this species. Nutritional values such as ash, fiber, protein, fat, and carbohydrate contents were investigated, and phytochemical screenings with different reagents showed the presence of flavonoids, glycosides, saponin glycosides, phenolic compounds, steroids, tannins, and terpenoids. Our results also revealed that the water fraction had the highest antioxidant activity compared to the methanol extract and other fractions. The methanol and the fractionated extracts (hexane, chloroform, ethyl acetate, and water) ofP. macrocarpaseeds were also investigated for their cytotoxic effects on selected human cancer cells lines (MCF-7, HT-29, MDA-MB231, Ca Ski, and SKOV-3) and a normal human fibroblast lung cell line (MRC-5). Information from this study can be applied for future pharmacological and therapeutic evaluations of the species, and may assist in the standardization for quality, purity, and sample identification. To the best of our knowledge, this is the first report on the phytochemical screening and cytotoxic effect of the crude and fractionated extracts ofP. macrocarpaseeds on selected cells lines.

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The antioxidant, aged garlic extract, exerts cytotoxic effects on wild-type and multidrug-resistant human cancer cells by altering mitochondrial permeability

International Journal of Oncology ◽

10.3892/ijo.2018.4452 ◽

2018 ◽

Cited By ~ 3

Author(s):

Shinji Ohkubo ◽

Lisa Dalla Via ◽

Silvia Grancara ◽

Yuta Kanamori ◽

A�da Garc�a-Arg�ez ◽

...

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Multidrug Resistant ◽

Garlic Extract ◽

Wild Type ◽

Aged Garlic Extract ◽

Cytotoxic Effects ◽

Mitochondrial Permeability ◽

Human Cancer Cells ◽

Aged Garlic

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Inhibition of NADPH Oxidases Activity by Diphenyleneiodonium Chloride as a Mechanism of Senescence Induction in Human Cancer Cells

Antioxidants ◽

10.3390/antiox9121248 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1248

Author(s):

Katarzyna Piszczatowska ◽

Dorota Przybylska ◽

Ewa Sikora ◽

Grażyna Mosieniak

Keyword(s):

Cancer Cells ◽

Therapeutic Potential ◽

Human Cancer ◽

Cell Metabolism ◽

Human Colon ◽

Nadph Oxidases ◽

Human Colon Cancer ◽

Inhibition Of Proliferation ◽

Human Cancer Cells ◽

Mcf 7

NADPH oxidases (NOX) are commonly expressed ROS-producing enzymes that participate in the regulation of many signaling pathways, which influence cell metabolism, survival, and proliferation. Due to their high expression in several different types of cancer it was postulated that NOX promote tumor progression, growth, and survival. Thus, the inhibition of NOX activity was considered to have therapeutic potential. One of the possible outcomes of anticancer therapy, which has recently gained much interest, is cancer cell senescence. The induction of senescence leads to prolonged inhibition of proliferation and contributes to tumor growth restriction. The aim of our studies was to investigate the influence of low, non-toxic doses of diphenyleneiodonium chloride (DPI), a potent inhibitor of flavoenzymes including NADPH oxidases, on p53-proficient and p53-deficient HCT116 human colon cancer cells and MCF-7 breast cancer cells. We demonstrated that the temporal treatment of HCT116 and MCF-7 cancer cells (both p53 wild-type) with DPI caused induction of senescence, that was correlated with decreased level of ROS and upregulation of p53/p21 proteins. On the contrary, in the case of p53−/− HCT116 cells, apoptosis was shown to be the prevailing effect of DPI treatment. Thus, our studies provided a proof that inhibiting ROS production, and by this means influencing ROS sensitive pathways, remains an alternative strategy to facilitate so called therapy-induced senescence in cancers.

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Multicomponent and 1,3-dipolar cycloaddition synthesis of triazole- and isoxazole-acridinedione/xanthenedione heterocyclic hybrids: Cytotoxic effects on human cancer cells

Journal of Molecular Structure ◽

10.1016/j.molstruc.2020.128325 ◽

2020 ◽

Vol 1217 ◽

pp. 128325 ◽

Cited By ~ 1

Author(s):

Abdelkader Naouri ◽

Amar Djemoui ◽

Mouhamad Ridha Ouahrani ◽

Mokhtar Boualem Lahrech ◽

Najet Lemouari ◽

...

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Dipolar Cycloaddition ◽

Cytotoxic Effects ◽

Human Cancer Cells

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Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species

Biomolecules ◽

10.3390/biom10030377 ◽

2020 ◽

Vol 10 (3) ◽

pp. 377

Author(s):

Iván González-Chavarría ◽

Felix Duprat ◽

Francisco J. Roa ◽

Nery Jara ◽

Jorge R. Toledo ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cancer Cells ◽

Human Cancer ◽

Ros Generation ◽

Active Components ◽

Total Extract ◽

Human Cancer Cells ◽

Mitochondrial Superoxide ◽

Mitochondrial Membrane Depolarization ◽

Mcf 7

Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. β-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (µg/mL) of 40, 4.7, and 5 µg/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The β-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-β-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 µM, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the β-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.

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