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ABSTRACT Introduction: Chemotherapy is one of the preferred mode of treatment of malignancies, but is complicated by the expression of diverse resistance mechanisms of cancer cells. Methods: In the present [...]

ABSTRACT Background: The low abundant cajanin stilbene acid (CSA) from Pigeon Pea (Cajanus cajan) has been shown to kill estrogen receptor α positive cancer cells in vitro and in vivo. [...]

ABSTRACT Although cancer stem-like cells (CSCs) are rare, they can enter a non-proliferative or dormant state and resist therapy. Furthermore, quiescent CSCs are responsible for metastases that can appear after [...]

ABSTRACT Introduction: Resistance of cancer cells to chemotherapy has become a worldwide concern. Naturally occuring isoflavonoids possess a variety of biological activities including anti-cancer effects. The present study was aimed [...]

ABSTRACT Background: Resistance of cancer to chemotherapy remains a challenging issue for scientists as well as physicians. Naturally occurring xanthones possess a variety of biological activities such as antiinflammatory, anti-bacterial, [...]

ARTICLE INFO Keywords: Benzophenones Plants Cytotoxicity Cell cycle distribution Mitochondrial membrane potential ABSTRACT Introduction: The emergence of drug-resistant cancer cells drastically reduces the efficacy of many antineoplasic agents and, consequently, [...]

Introduction: Resistance of cancer to chemotherapy is a main cause in treatment failure. Naturally occurring chalcones possess a wide range of biological activities including anti-cancer effects. In this work, we evaluated the antiproliferative activity of three chalcones [4'-hydroxy-2',6'-dimethoxychalcone (1), cardamomin (2), 2',4'-dihydroxy-3',6'-dimethoxychalcone (3)], and four flavanones [(S)-(-)-pinostrobin (4), (S)-(-)-onysilin (5) and alpinetin (6)] toward nine cancer cell lines amongst which were multidrug resistant (MDR) types., Methods: The resazurin reduction assay was used to detect the antiproliferative activity of the studied samples whilst flow cytometry for the mechanistic studies of the most active molecule (1)., Results: IC50 values in a range of 2.54 μM against CEM/ADR5000 leukemia cells to 58.63 μM toward hepatocarcinoma HepG2 cells were obtained with 1. The lowest IC50 values of 8.59 μM for 2 and 10.67 μM for 3 were found against CCRF-CEM cells leukemia cells, whilst the corresponding values were above 80 μM for 4 and 6. P-glycoprotein-expressing and multidrug-resistant CEM/ADR5000 cells were much more sensitive toward compound 1 than toward doxorubicin and low cross-resistance or even collateral sensitivity was observed in other drug-resistent cell lines to this compound. Normal liver AML12 cells were more resistant to the studied compounds than HepG2 liver cancer cells, indicating tumor specificity at least to some extent. Compound 1 arrested the cell cycle between Go/G1 phase, strongly induced apoptosis via disrupted mitochondrial membrane potential (MMP) and increased production of reactive oxygen species (ROS) in the studied leukemia cell line., Conclusions: Chalcone 1 was the best tested cytotoxic molecule and further studies will be performed in order to envisage its possible use in the fight against multifactorial resistant cancer cells., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Introduction: The emergence of drug-resistant cancer cells drastically reduces the efficacy of many antineoplasic agents and, consequently, increases the frequency of therapeutic failure. Benzophenones are known to display many pharmacological properties including cytotoxic activities. The present study was aimed at investigating the cytotoxicity and the modes of action of four naturally occurring benzophenones 2,2',5,6'-tetrahydroxybenzophenone (1), isogarcinol (2), isoxanthochymol (3) and guttiferone E (4) on a panel of eleven cancer cell lines including various sensitive and drug-resistant phenotypes., Methods: The cytotoxicity of the compounds was determined using a resazurin reduction assay, whereas the caspase-Glo assay was used to detect the activation of caspases 3/7, caspase 8 and caspase 9 in cells treated with compounds 2-4. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells, analysis of mitochondrial membrane potential (MMP) as well as measurement of reactive oxygen species (ROS)., Results: The four tested benzophenones inhibited the proliferation of all tested cancer cell lines including sensitive and drug-resistant phenotypes. Collateral sensitivity of cancer cells to compounds 1-4 was generally better than to doxorubicin. Compound 2 showed the best activity with IC50 values below or around 1 μM against HCT116 colon carcinoma cells (p53+/+) (0.86 μM) and leukemia CCRF-CEM (1.38 μM) cell lines. Compounds 2-4 strongly induced apoptosis in CCRF-CEM cells via caspases 3/7, caspase 8 and caspase 9 activation and disruption of MMP., Conclusions: The studied benzophenones are cytotoxic compounds that deserve more detailed exploration in the future, to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes., (Copyright © 2013 Elsevier GmbH. All rights reserved.)