Quercetin Enhances the Antitumor Activity of Trichostatin A through Upregulation of p53 Protein Expression In Vitro and In Vivo

Chan, Shun‐Yu; Yang, Nae-Cherng; Huang, Chin-Shiu; Liao, Jiunn‐Wang; Yeh, Shu-Lan

doi:10.1371/journal.pone.0054255

Cited by 71 publications

(58 citation statements)

References 39 publications

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“…This corroborates with findings from earlier studies which showed that treatment with combination of GO and AgNPs and combination of salinomycin 34,40,87 Combination of TSA and quercetin induced apoptosis through p53 activation in mouse tumors compared to control or cells treated with TSA alone. 88 The results from previous studies and the findings of the present study show that the combination of rGO-Ag and TSA induces cell death in a p53-dependent manner in human ovarian cancer cells.…”

Section: Rgo-ag and Tsa Cause Mitochondrial Dysfunctionsupporting

confidence: 73%

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Zhang¹,

Huang²,

Zhang³

et al. 2017

IJN

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Background Recently, there has been much interest in the field of nanomedicine to improve prevention, diagnosis, and treatment. Combination therapy seems to be most effective when two different molecules that work by different mechanisms are combined at low dose, thereby decreasing the possibility of drug resistance and occurrence of unbearable side effects. Based on this consideration, the study was designed to investigate the combination effect of reduced graphene oxide-silver nanoparticles (rGO-AgNPs) and trichostatin A (TSA) in human ovarian cancer cells (SKOV3). Methods The rGO-AgNPs were synthesized using a biomolecule called lycopene, and the resultant product was characterized by various analytical techniques. The combination effect of rGO-Ag and TSA was investigated in SKOV3 cells using various cellular assays such as cell viability, cytotoxicity, and immunofluorescence analysis. Results AgNPs were uniformly distributed on the surface of graphene sheet with an average size between 10 and 50 nm. rGO-Ag and TSA were found to inhibit cell viability in a dose-dependent manner. The combination of rGO-Ag and TSA at low concentration showed a significant effect on cell viability, and increased cytotoxicity by increasing the level of malondialdehyde and decreasing the level of glutathione, and also causing mitochondrial dysfunction. Furthermore, the combination of rGO-Ag and TSA had a more pronounced effect on DNA fragmentation and double-strand breaks, and eventually induced apoptosis. Conclusion This study is the first to report that the combination of rGO-Ag and TSA can cause potential cytotoxicity and also induce significantly greater cell death compared to either rGO-Ag alone or TSA alone in SKOV3 cells by various mechanisms including reactive oxygen species generation, mitochondrial dysfunction, and DNA damage. Therefore, this combination chemotherapy could be possibly used in advanced cancers that are not suitable for radiation therapy or surgical treatment and facilitate overcoming tumor resistance and disease progression.

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Section: Rgo-ag and Tsa Cause Mitochondrial Dysfunctionsupporting

confidence: 73%

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Zhang¹,

Huang²,

Zhang³

et al. 2017

IJN

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“…As A549 line has been widely used as a model system to study human alveolar carcinoma, cytotoxic profile of flavonoids in these cells was previously characterized with the results very similar to those measured in our work. Indeed, the IC 50 value of 72.2 µM for quercetin is close to the inhibitory constants published by Loizzo et al (26), Tan et al (27)(28)(29), Robaszkiewicz et al (30), and Chan et al (31); and IC 50 values more than 100 µM were previously reported for fisetin (32), hesperetin (33-35), luteolin (32,36), chrysin (35), baicalein (34), daidzein (37), and genistein (38). Based on our results presented in this article, cytotoxic activity profiles of flavonoids were rather similar for both A549 and HCC-44 lung cancer lines, despite the gender difference of initial origin of these cells.…”

Section: Discussionsupporting

confidence: 86%

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

et al. 2017

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Abstract. Lung cancer is the malignant disorder associated with a high number of fatalities in women and men worldwide. Despite continuous improvements in diagnostic strategies and therapeutic modalities over the past decades, the prognosis and survival rate of patients suffering from lung cancer are still unsatisfactory and suggest the requirement for further molecular studies with different lung cancer models. In the present study, the anticancer action of two methylated metabolites of quercetin, isorhamnetin and tamarixetin, was assessed by studying their antiproliferative and apoptosis-inducing potential in human lung adenocarcinoma cell lines, A549 and HCC-44. Both methylquercetins decreased the viability of lung cancer cells at doses significantly lower than those effective for parent quercetin. The IC 50 values measured for isorhamnetin were 26.6 and 15.9 µM in A549 and HCC-44 cells, respectively. For tamarixetin, the IC 50 values were 19.6 and 20.3 µM in A549 and HCC-44 cells, respectively. These results were many-fold lower than the respective values for quercetin (72.2 and 107.6 µM for A549 and HCC-44 cells, respectively). Based on the activation of caspase family members, both metabolites induced apoptotic cell death in the tested cell lines, predominantly via the extrinsic pathway in A549 cells and in both intrinsic and extrinsic pathways in HCC-44 cells. As A549 and HCC-44 lines were originally established from a male and female patient, current data may suggst some gender differences in the action of quercetin derivatives. Addition of a methyl group in the 3'-or 4'-position of the B-ring of quercetin significantly increased the anticancer activity of this flavonol towards lung adenocarcinoma cells, which demonstrated that these compounds may be considered as potential novel candidates for the development of future chemotherapeutics in the fight against lung cancer.

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“…Previous studies have reported that a combination of HDACIs, such as TSA combined with curcumin, produced significant antiproliferative and apoptotic effects compared with either agent alone. 40 The combination of quercetin and TSA significantly increased the cytotoxic effect in A549 cells, 41 whereas that of TSA and PdNPs produced a significant inhibitory effect on cell survival and HDAC activity in HeLa cells. In order to determine the correlation between cell viability and HDAC activity, we first evaluated the combinatorial effect of TUB-A and PdNPs on cell viability and HDAC activity in MDA-MB-231 human breast cancer cells.…”

Section: Results and Discussion Synthesis And Characterization Of Pdnpsmentioning

confidence: 99%

Combination of palladium nanoparticles and tubastatin-A potentiates apoptosis in human breast cancer cells: a novel therapeutic approach for cancer

Yuan¹,

Peng²,

Gurunathan³

2017

IJN

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Background Breast cancer is the most common malignant disease that occurs in women. Histone deacetylase (HDAC) inhibition has recently emerged as an effective and attractive target for the treatment of cancer. The aim of this study was to investigate the efficacy of a combined treatment of tubastatin A (TUB-A) and palladium nanoparticles (PdNPs) against MDA-MB-231 human breast cancer cells using two different cytotoxic agents that work by two different mechanisms, thereby decreasing the probability of chemoresistance in cancer cells and increasing the efficacy of toxicity, to provide efficient therapy for advanced stage of cancer without any undesired side effects. Methods PdNPs were synthesized using a novel biomolecule called R-phycoerythrin and characterized using various analytical techniques. The combinatorial effect of TUB-A and PdNPs was assessed by various cellular and biochemical assays and also by gene expression analysis. Results The biologically synthesized PdNPs had an average size of 25 nm and were spherical in shape. Treatment of MDA-MB-231 human breast cancer cells with TUB-A or PdNPs showed a dose-dependent effect on cell viability. The combination of 4 μM TUB-A and 4 μM PdNPs had a significant inhibitory effect on cell viability compared with either TUB-A or PdNPs alone. The combinatorial treatment also had a more pronounced effect on the inhibition of HDAC activity and enhanced apoptosis by regulating various cellular and biochemical changes. Conclusion Our results suggest that there was a strong synergistic interaction between TUB-A and PdNPs in increasing apoptosis in human breast cancer cells. These data provide an important preclinical basis for future clinical trials on this drug combination. This combinatorial treatment increased therapeutic potentials, thereby demonstrating a relevant targeted therapy for breast cancer. Furthermore, we have provided the first evidence for the combinatorial effect and mechanism of toxicity of TUB-A and PdNPs in human breast cancer cells. The novelties of the study were identification of a combination therapy that consists of suitable therapeutic molecules that kill cancer cells and also exploration of two different possible mechanisms involved to reduce chemoresistance in cancer cells.

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Quercetin Enhances the Antitumor Activity of Trichostatin A through Upregulation of p53 Protein Expression In Vitro and In Vivo

Cited by 71 publications

References 39 publications

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

Combination of palladium nanoparticles and tubastatin-A potentiates apoptosis in human breast cancer cells: a novel therapeutic approach for cancer

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