Cinnamic acid derivatives as chemosensitising agents against DOX-treated lung cancer cells – Involvement of carbonyl reductase 1

Koczurkiewicz-Adamczyk, Paulina; Piska, Kamil; Gunia‐Krzyżak, Agnieszka; Bucki, Adam; Jamrozik, Marek; Lorenc, Ewelina; Ryszawy, Damian; Wójcik-Pszczoła, Katarzyna; Michalik, Marta; Marona, Henryk; Kołaczkowski, Marcin; Pękala, Elżbieta

doi:10.1016/j.ejps.2020.105511

Cited by 20 publications

(20 citation statements)

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“…To determine antiproliferative activity, the cells were seeded onto 12-well plates (5 × 10 3 cells/well) and incubated for 24 h. After 24, 48 and 72 h of incubation with or without usnic acid enantiomers (0–100 µg/mL), cell number was determined using crystal violet assay, as described previously [ 33 ]. Briefly, the cells were washed with PBS and fixed with 3.7% formaldehyde.…”

Section: Methodsmentioning

confidence: 99%

A Comparative Survey of Anti-Melanoma and Anti-Inflammatory Potential of Usnic Acid Enantiomers—A Comprehensive In Vitro Approach

et al. 2021

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Usnic acid (UA) is a chiral lichen metabolite with an interesting pharmacological profile. The aim of this study was to compare the anti-melanoma effect of (+)-UA and (−)-UA in an in vitro model by studying their impact on the cells as well as the processes associated with cancer progression. The effect of UA enantiomers on the viability, proliferation, and invasive potential of three melanoma cell lines (HTB140, A375, WM793) was evaluated. Their interaction with a chemotherapeutic drug—doxorubicin was assessed by isobolographic analysis. Anti-inflammatory and anti-tyrosinase properties of (+)-UA and (−)-UA were also examined. Both UA enantiomers dose- and time-dependently decreased the viability of all three melanoma cell lines. Their synergistic effect with doxorubicin was observed on A375 cells. (+)-Usnic acid at a sub-cytotoxic dose strongly inhibited melanoma cells migration. Both UA enantiomers decreased the release of pro-inflammatory mediators. The cytotoxic effect of (+)-UA and (−)-UA depends greatly on the melanoma cell type; however, the overall anti-melanoma potential is perspective. Our results indicate that the strategy of combining usnic acid enantiomers with cytostatic drugs may be an interesting option to consider in combating melanoma; however, further studies are required.

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Section: Methodsmentioning

confidence: 99%

A Comparative Survey of Anti-Melanoma and Anti-Inflammatory Potential of Usnic Acid Enantiomers—A Comprehensive In Vitro Approach

et al. 2021

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“…In conclusion, we presented new beneficial effects of three CA derivatives with previously proven DOX-chemosensitizing activity [22]. Apart from the beneficial antitumor activity, these derivatives could protect myocardial cells against the toxic effects of DOX.…”

Section: Discussionmentioning

confidence: 76%

“…The compounds used for the study were biologically active CA (cinnamic acid) derivatives previously synthesized by our group, with proven inhibitory potential for the CBR1 enzyme [22][23][24][25][26]. This paper presents the cardioprotective activity of the three most active derivatives: 5, 10, and 15.…”

Section: Resultsmentioning

confidence: 99%

“…Their mechanism of action is connected to CBR1 enzyme inhibition and inhibition of DOXol formation. Here we present the most promising CA derivatives tested in our group (5, 10, and 15) for cardioprotective activity [22]. Limiting the production of DOXol may protect the heart muscle from the adverse effects of DOX.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we showed that CA derivatives, which were designed and synthetized by our group, exhibited chemosensitizing activity in DOX-treated A549 lung cancer cells. They were found to interact with active sites of the CBR1 enzyme and decrease DOXol formation [22].…”

Section: Introductionmentioning

confidence: 99%

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Cinnamic Acid Derivatives as Cardioprotective Agents against Oxidative and Structural Damage Induced by Doxorubicin

Koczurkiewicz-Adamczyk

Klaś

Gunia‐Krzyżak

et al. 2021

IJMS

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Doxorubicin (DOX) is a widely used anticancer drug. However, its clinical use is severely limited due to drug-induced cumulative cardiotoxicity, which leads to progressive cardiomyocyte dysfunction and heart failure. Enormous efforts have been made to identify potential strategies to alleviate DOX-induced cardiotoxicity; however, to date, no universal and highly effective therapy has been introduced. Here we reported that cinnamic acid (CA) derivatives exert a multitarget protective effect against DOX-induced cardiotoxicity. The experiments were performed on rat cardiomyocytes (H9c2) and human induced-pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs) as a well-established model for cardiac toxicity assessment. CA derivatives protected cardiomyocytes by ameliorating DOX-induced oxidative stress and viability reduction. Our data indicated that they attenuated the chemotherapeutic’s toxicity by downregulating levels of caspase-3 and -7. Pre-incubation of cardiomyocytes with CA derivatives prevented DOX-induced motility inhibition in a wound-healing assay and limited cytoskeleton rearrangement. Detailed safety analyses—including hepatotoxicity, mutagenic potential, and interaction with the hERG channel—were performed for the most promising compounds. We concluded that CA derivatives show a multidirectional protective effect against DOX-induced cardiotoxicity. The results should encourage further research to elucidate the exact molecular mechanism of the compounds’ activity. The lead structure of the analyzed CA derivatives may serve as a starting point for the development of novel therapeutics to support patients undergoing DOX therapy.

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Ethacrynic acid and cinnamic acid combination exhibits selective anticancer effects on K562 chronic myeloid leukemia cells

Yenigül

Akçok

2022

Mol Biol Rep

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Cinnamic acid derivatives as chemosensitising agents against DOX-treated lung cancer cells – Involvement of carbonyl reductase 1

Cited by 20 publications

References 51 publications

A Comparative Survey of Anti-Melanoma and Anti-Inflammatory Potential of Usnic Acid Enantiomers—A Comprehensive In Vitro Approach

A Comparative Survey of Anti-Melanoma and Anti-Inflammatory Potential of Usnic Acid Enantiomers—A Comprehensive In Vitro Approach

Cinnamic Acid Derivatives as Cardioprotective Agents against Oxidative and Structural Damage Induced by Doxorubicin

Ethacrynic acid and cinnamic acid combination exhibits selective anticancer effects on K562 chronic myeloid leukemia cells

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