Acalypha wilkesiana extracts induce apoptosis by causing single strand and double strand DNA breaks

Lim, Su-Wen; Ting, Kang Nee; Bradshaw, Tracey D.; Allaudin, Zeenathul Nazariah; Wiart, Christophe; Khoo, Teng-Jin; Lim, Kuan‐Hon; Loh, Hwei‐San

doi:10.1016/j.jep.2011.10.005

Cited by 31 publications

(31 citation statements)

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“…The palm oil derived alpha-, gamma- and delta-tocotrienol isomers were extracted and supplied in palm vitamin E isomers kit by Davos Life Science Pte Ltd (Singapore). The human lung adenocarcinoma (A549), grade IV glioblastoma (U87MG) and normal lung fibroblast (MRC5) were grown and maintained at the similar conditions as previously published papers [ 20 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Lim

Loh

Ting

et al. 2014

BMC Complement Altern Med

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BackgroundTocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched.MethodsThe cytotoxic effects of alpha-, gamma- and delta-tocotrienols in both A549 and U87MG cancer cells were first determined at the cell viability and morphological aspects. DNA damage types were then identified by comet assay and flow cytometric study was carried out to support the incidence of apoptosis. The involvements of caspase-8, Bid, Bax and mitochondrial membrane permeability (MMP) in the execution of apoptosis were further expounded.ResultsAll tocotrienols inhibited the growth of A549 and U87MG cancer cells in a concentration- and time-dependent manner. These treated cancer cells demonstrated some hallmarks of apoptotic morphologies, apoptosis was further confirmed by cell accumulation at the pre-G1 stage. All tocotrienols induced only double strand DNA breaks (DSBs) and no single strand DNA breaks (SSBs) in both treated cancer cells. Activation of caspase-8 leading to increased levels of Bid and Bax as well as cytochrome c release attributed by the disruption of mitochondrial membrane permeability in both A549 and U87MG cells were evident.ConclusionsThis study has shown that delta-tocotrienol, in all experimental approaches, possessed a higher efficacy (shorter induction period) and effectiveness (higher induction rate) in the execution of apoptosis in both A549 and U87MG cancer cells as compared to alpha- and gamma-tocotrienols. Tocotrienols in particular the delta isomer can be an alternative chemotherapeutic agent for treating lung and brain cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-469) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Lim

Loh

Ting

et al. 2014

BMC Complement Altern Med

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“…In some cases, the plant is also used to treat malaria, gastrointestinal problems [9], and potentially cancers [10, 11]. Previously, we found anti-MRSA and other antibacterial activities in the ethyl acetate and ethanol extracts of A. wilkesiana [12].…”

Section: Introductionmentioning

confidence: 99%

Reversal of Ampicillin Resistance in MRSA via Inhibition of Penicillin-Binding Protein 2a byAcalypha wilkesiana

Santiago

Pang

Lim

et al. 2014

BioMed Research International

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The inhibitory activity of a semipure fraction from the plant, Acalypha wilkesiana assigned as 9EA-FC-B, alone and in combination with ampicillin, was studied against methicillin-resistant Staphylococcus aureus (MRSA). In addition, effects of the combination treatment on PBP2a expression were investigated. Microdilution assay was used to determine the minimal inhibitory concentrations (MIC). Synergistic effects of 9EA-FC-B with ampicillin were determined using the fractional inhibitory concentration (FIC) index and kinetic growth curve assay. Western blot experiments were carried out to study the PBP2a expression in treated MRSA cultures. The results showed a synergistic effect between ampicillin and 9EA-FC-B treatment with the lowest FIC index of 0.19 (synergism ≤ 0.5). The presence of 9EA-FC-B reduced the MIC of ampicillin from 50 to 1.56 μg mL−1. When ampicillin and 9EA-FC-B were combined at subinhibitory level, the kinetic growth curves were suppressed. The antibacterial effect of 9EA-FC-B and ampicillin was shown to be synergistic. The synergism is due the ability of 9EA-FC-B to suppress the activity of PBP2a, thus restoring the susceptibility of MRSA to ampicillin. Corilagin was postulated to be the constituent responsible for the synergistic activity showed by 9EA-FC-B.

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“…However, A. cuspidata showed a MIC value of 97.65 µg/mL against S. aureus and catalytic antitopoisomerase II activity (at 50 μg/mL). The antitopoisomerase activity of Acalypha genus has not been described, although there is a report about the probable antitopoisomerase II activity of A. wilkesiana extracts, which induce apoptosis by single and double strand DNA breaks (Lim et al, 2011). Chemical studies of the Acalypha genus demonstrated the presence of sesquiterpenes and diterpenes (Siems et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Anticancer Potential of Eight Vegetal Species From the State of Oaxaca

León¹,

Herrera-Martínez²,

Ramirez-Mares³

et al. 2017

Afr J Tradit Complement Altern Med

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Background: Eight plant species from Oaxaca, some of them used in traditional medicine, were subjected to screening of several biological activities to provide data regarding their anticancer potential, although no scientific information is available about their pharmacological effects. Materials and methods: Methanol extracts from stems or roots of the eight plants were tested for antioxidant activity by the DPPH· method. Antimicrobial activity was determined using the agar diffusion method and the minimal inhibitory concentration (MIC) was obtained by broth dilution method. Antitopoisomerase activity was assessed using mutant strains of Saccharomyces cerevisiae JN362a, JN394, JN394t -1 , JN394t 2-4 and JN394t 2-5 . The mutagenic activity was evaluated using the Ames test (Salmonella typhimurium TA1535). Results:No extract showed significant antioxidant activity. The best antimicrobial activity was observed for Salpianthus arenarius (MIC 56.25 μg/mL) and Lantana achyranthifolia (MIC 78.12 μg/mL) against Staphylococcus aureus. Extracts of Acalypha cuspidata, Alloispermum integrifolium and L. achyranthifolia stems showed antitopoisomerase II activity with JN394 t-1 growth of -30.88±0.0%, -38.11±4.95%, and -70.97±12.02% respectively. Galium mexicanum stem extract showed antitopoisomerase I activity with growth of 35.31±6.36% on the same mutant strain. All plant extracts were non-mutagenic. Fractionation of A. cuspidata extract led to identification of two subfractions with antitopoisomerase I and II activity at 154μg/mL (Positive controls 50 and 100μg/mL). Conclusion: Methanol extracts of A. cuspidata, A. integrifolium, G. mexicanum, and L. achyranthifolia stems showed antitopoisomerase and non-mutagenic activities, and consequently could be promising as a source of anticancer drugs.

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Acalypha wilkesiana extracts induce apoptosis by causing single strand and double strand DNA breaks

Abstract: The extracts (especially ethyl acetate and hexane) of Acalypha wilkesiana possess valuable cytotoxic effects that trigger apoptosis in U87MG and A549 cancer cells through induction of DNA SSBs and DSBs.

Cited by 31 publications

References 59 publications

Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Reversal of Ampicillin Resistance in MRSA via Inhibition of Penicillin-Binding Protein 2a byAcalypha wilkesiana

Evaluation of Anticancer Potential of Eight Vegetal Species From the State of Oaxaca

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