Cytotoxicity of gemcitabine enhanced by polyphenolics from<i>Aronia melanocarpa</i>in pancreatic cancer cell line AsPC-1

Thani, Noorr Azela Abdullah; Keshavarz, Sholeh; Lwaleed, Bashir A.; Cooper, Alan; Rooprai, Harcharan K.

doi:10.1136/jclinpath-2013-202075

Cited by 18 publications

(16 citation statements)

References 25 publications

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“…The lowest IC 50 values were observed forL2OB cells. Thani et al [45] reported that A. melanocarpa extract enhanced the cytotoxicity of gemcitamibe chemotherapy medication in the human pancreatic adenocarcinoma cell line ASPC-1.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and DNA-Damaging Effects of Aronia melanocarpa, Cornus mas, and Chaenomeles superba Leaf Extracts on the Human Colon Adenocarcinoma Cell Line Caco-2

Efenberger-Szmechtyk

Nowak

2020

Antioxidants

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Aronia melanocarpa, Cornus mas, and Chaenomeles superba leaf extracts contain large amounts of bioactive compounds—mainly polyphenols, which possess many health benefits including anti-cancer properties. Here, we investigate the biological effects of A. melanocarpa, C. mas, and C. superba leaf extracts on the human colon adenocarcinoma cell line Caco-2. The antiproliferative activity of the extracts was measured using the MTT assay. The most cytotoxic extract was C. mas (IC50 = 0.60%). The extracts caused morphological changes in the Caco-2 cells, including partial detachment of cells, necrotic cells, chromatin condensation, cytoplasmic vacuolization, cell nuclei lysis, and nucleus fragmentation. The DNA damage in the Caco-2 cells after exposure to the leaf extracts was measured using the alkaline comet assay. The extracts increased DNA damage in a concentration dependent manner. However, at lower non-cyto- and non-genotoxic (IC0) concentrations the extracts induced DNA repair in Caco-2 cells after exposure to hydrogen peroxide. In conclusion, the results of these studies suggest that A. melanocarpa, C. mas and C. superba leaf extracts can show anticancer activity. However, further research is required on the mechanisms of anti-cancer activity by these extracts, with the application of more advanced and wide-ranging techniques including in vivo experiments.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic and DNA-Damaging Effects of Aronia melanocarpa, Cornus mas, and Chaenomeles superba Leaf Extracts on the Human Colon Adenocarcinoma Cell Line Caco-2

Efenberger-Szmechtyk

Nowak

2020

Antioxidants

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“…In the present study, the cytotoxic properties of either gemcitabine or doxorubicin, in presence or not of quercetin, were analyzed in AsPC-1 and HepG2 cell lines respectively, in order to evaluate any supra-additional effect. MDR1-inhibiting agents are known to be pharmacologically active in vitro in a concentration range from 1 to 15 μg /ml [35]. A range of 1-50 μM of the micronutrient quercetin was therefore chosen in this study, as minimally cytotoxic doses.…”

Section: Plos Onementioning

confidence: 99%

Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1

et al. 2020

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The impact of cancer on lifespan is significantly increasing worldwide. Enhanced activity of drug efflux pumps and the incidences of the tumor microenvironment such as the apparition of a hypoxic gradient inside of the bulk tumor, are the major causes of chemotherapy failure. For instance, expression of Hypoxia-inducible factor (HIF-1α) has been associated with metastasis, resistance to chemotherapy and reduced survival rate. One of the current challenges to fight against cancer is therefore to find new molecules with therapeutic potential that could overcome this chemoresistance. In the present study, we focused on the bioactive plant flavonoid quercetin, which has strong antioxidant and anti-proliferative properties. We examined the efficacy of combined treatments of quercetin and the anti-cancer drugs gemcitabine and doxorubicin, known to specifically act on human pancreatic and hepatic cancer cells, respectively. Moreover, our study aimed to investigate more in-depth the implication of the multidrug transporter MDR1 and HIF-1α n chemoresistance and if quercetin could act on the activity of the drug efflux pumps and the hypoxia-associated effects. We observed that the anti-cancer drugs, were more effective when administered in combination with quercetin, as shown by an increased percentage of dead cells up to 60% in both 2D and 3D cultures. In addition, our results indicated that the combination of anti-cancer drugs and quercetin downregulated the expression of HIF-1α and increased the expression levels of the regulator of apoptosis p53. Moreover, we observed that quercetin could inhibit the efflux activity of MDR1. Finally, our in vitro study suggests that the efficiency of the chemotherapeutic activity of known anti-cancer drugs might be significantly increased upon combination with quercetin. This flavonoid may therefore be a promising pharmacological agent for novel combination therapy since it potentializes the cytotoxic activity of gemcitabine and doxorubicin on by targeting the chemoresistance developed by the pancreatic and liver cancer cells respectively.

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“…Studies with animal models and in vitro models show that chokeberry extracts and other products made from aronia fruit are effective in the prevention of carcinogenic occurrences due to their strong antioxidative action (Gąsiorowski and others ; Malik and others ; Zhao and others ; Lala and others ; Bermúdez‐Soto and others ,b; Shih and others ; Olas and others ; Balansky and others ; Kędzierska and others , ,b; Rugină and others ; Sharif and others ; Li and others ; Pratheeshkumar and others ; Thani and others ). The anticarcinogenic effect of aronia berry products is related to the antioxidative properties of polyphenolic compounds which protect healthy cells from oxidative damage induced by free radicals (Shih and others ), pro‐apoptotic action which enables the death of cells with carcinogenic changes (Rugină and others ; Sharif and others ), and the ability to arrest the cell cycle of tumor cells (Malik and others ; Zhao and others ; Bermúdez‐Soto and others ,b; Sharif and others ).…”

Section: Chokeberries and Their Products In The Prevention And Treatmmentioning

confidence: 99%

“…Chokeberry extract has pro‐apoptotic properties (Sharif and others ; Thani and others ). Cyanidin glycosides isolated from aronia fruit extract have been reported to induce an accumulation of peroxides in HeLa tumor cell culture which triggers apoptotic pathways in these cells (Rugină and others ; Sharif and others ).…”

Section: Chokeberries and Their Products In The Prevention And Treatmmentioning

confidence: 99%

“…It should be emphasized that chokeberry extract supports the action of anticancer drugs used in the treatment of some types of cancer. For example, Thani and others () have revealed that the extract increased the effectiveness of gemcitabine against growth of the pancreatic cell line (AsPC‐1 cell line). Moreover, based on the available data, it can be concluded that the consumption of chokeberry products may be effective for the protection against side effects of drugs used in chemotherapy (such as cisplatin).…”

Section: Chokeberries and Their Products In The Prevention And Treatmmentioning

confidence: 99%

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Chokeberries (Aronia melanocarpa) and Their Products as a Possible Means for the Prevention and Treatment of Noncommunicable Diseases and Unfavorable Health Effects Due to Exposure to Xenobiotics

Borowska

Brzóska

2016

Comp Rev Food Sci Food Safe

102

155

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Aronia melanocarpa berries (chokeberries) constitute a very rich source of numerous substances exerting a beneficial impact on health, including mainly polyphenols (proanthocyanidins, anthocyanins, flavonoids, and phenolic acids), possessing antioxidative, anti-inflammatory, antiviral, anticancer, antiatherosclerotic, hypotensive, antiplatelet, and antidiabetic properties. Thus, the consumption of products made from chokeberries is of vital importance for health maintenance and protection. Nowadays, due to the growing prevalence of noncommunicable diseases and ubiquitous human exposure to numerous man-made and naturally occurring toxic substances, some of which are dangerous even at low amounts, it is very important to look for effective means of health protection. An important role in this regard may be played by A. melanocarpa berries; however, up to now the attention of scientists, nutritionists, and health practitioners has been focused mainly on the effectiveness of chokeberry products in the prevention and treatment of noncommunicable diseases, while only little attention has been paid to the possibility of their use to counteract the adverse health effects of exposure to xenobiotics. That is why in this review article the main interest has been focused on the possibility of using chokeberries in the protection against unfavorable health effects caused by the action of substances to which humans may be exposed environmentally and/or occupationally. The available experimental data indicate that not only the fruit but also the leaves of A. melanocarpa and their products may be effective means for prevention and treatment of the effects of toxic action of some xenobiotics in humans; however, further studies on this subject are necessary.

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Cytotoxicity of gemcitabine enhanced by polyphenolics fromAronia melanocarpain pancreatic cancer cell line AsPC-1

Abstract: The implication of this study, using single cancer cell line, is that chemotherapy (at least with gemcitabine) might be usefully augmented with the use of micronutrients such as chokeberry extract.

Cited by 18 publications

References 25 publications

Cytotoxic and DNA-Damaging Effects of Aronia melanocarpa, Cornus mas, and Chaenomeles superba Leaf Extracts on the Human Colon Adenocarcinoma Cell Line Caco-2

Cytotoxic and DNA-Damaging Effects of Aronia melanocarpa, Cornus mas, and Chaenomeles superba Leaf Extracts on the Human Colon Adenocarcinoma Cell Line Caco-2

Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1

Chokeberries (Aronia melanocarpa) and Their Products as a Possible Means for the Prevention and Treatment of Noncommunicable Diseases and Unfavorable Health Effects Due to Exposure to Xenobiotics

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