Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin
In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. C...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/21/3889 |
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| author | Jerry D. Monroe Denis Hodzic Matthew H. Millay Blaine G. Patty Michael E. Smith |
| author_facet | Jerry D. Monroe Denis Hodzic Matthew H. Millay Blaine G. Patty Michael E. Smith |
| author_sort | Jerry D. Monroe |
| collection | DOAJ |
| description | In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. Cellular viability was measured using the MTT assay. A scratch assay was used to measure cell migration and fluorescent spectrophotometry to measure reactive oxygen species (ROS) production. Western blots and luminescence assays were used to measure the expression and activity of apoptosis-inducing factor (AIF), caspases-3/7, -8, -9, and -12, c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK), and proto-oncogene tyrosine-protein kinase (Src). A zebrafish model was used to evaluate auditory effects. Cisplatin, the curcuminoids, and their combinations had similar effects on cell viability (IC<sub>50</sub> values: 2−16 μM) and AIF, caspase-12, JNK, MAPK, and Src expression, while caspase-3/7, -8, and -9 activity was unchanged or decreased. Cisplatin increased ROS yield (1.2-fold), and curcuminoid and combination treatments reduced ROS (0.75−0.85-fold). Combination treatments reduced A549 migration (0.51−0.53-fold). Both curcuminoids reduced auditory threshold shifts induced by cisplatin. In summary, cisplatin and the curcuminoids might cause cell death through AIF and caspase-12. The curcuminoids may potentiate cisplatin’s effect against A549 migration, but may counteract cisplatin’s effect to increase ROS production. The curcuminoids might also prevent cisplatin ototoxicity. |
| first_indexed | 2024-12-20T02:08:24Z |
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| id | doaj.art-ef35818d7762451598aaab723c8e3cfe |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T02:08:24Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ef35818d7762451598aaab723c8e3cfe2022-12-21T19:57:07ZengMDPI AGMolecules1420-30492019-10-012421388910.3390/molecules24213889molecules24213889Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with CisplatinJerry D. Monroe0Denis Hodzic1Matthew H. Millay2Blaine G. Patty3Michael E. Smith4Department of Biology, Western Kentucky University, 1906 College Heights Boulevard, #11080, Bowling Green, KY 42101-1080, USADepartment of Biology, Western Kentucky University, 1906 College Heights Boulevard, #11080, Bowling Green, KY 42101-1080, USADepartment of Biology, Western Kentucky University, 1906 College Heights Boulevard, #11080, Bowling Green, KY 42101-1080, USADepartment of Biology, Western Kentucky University, 1906 College Heights Boulevard, #11080, Bowling Green, KY 42101-1080, USADepartment of Biology, Western Kentucky University, 1906 College Heights Boulevard, #11080, Bowling Green, KY 42101-1080, USAIn this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. Cellular viability was measured using the MTT assay. A scratch assay was used to measure cell migration and fluorescent spectrophotometry to measure reactive oxygen species (ROS) production. Western blots and luminescence assays were used to measure the expression and activity of apoptosis-inducing factor (AIF), caspases-3/7, -8, -9, and -12, c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK), and proto-oncogene tyrosine-protein kinase (Src). A zebrafish model was used to evaluate auditory effects. Cisplatin, the curcuminoids, and their combinations had similar effects on cell viability (IC<sub>50</sub> values: 2−16 μM) and AIF, caspase-12, JNK, MAPK, and Src expression, while caspase-3/7, -8, and -9 activity was unchanged or decreased. Cisplatin increased ROS yield (1.2-fold), and curcuminoid and combination treatments reduced ROS (0.75−0.85-fold). Combination treatments reduced A549 migration (0.51−0.53-fold). Both curcuminoids reduced auditory threshold shifts induced by cisplatin. In summary, cisplatin and the curcuminoids might cause cell death through AIF and caspase-12. The curcuminoids may potentiate cisplatin’s effect against A549 migration, but may counteract cisplatin’s effect to increase ROS production. The curcuminoids might also prevent cisplatin ototoxicity.https://www.mdpi.com/1420-3049/24/21/3889cancercurcuminoidcisplatinzebrafishreactive oxygen speciesauditory evoked potentialapoptosiscell migration |
| spellingShingle | Jerry D. Monroe Denis Hodzic Matthew H. Millay Blaine G. Patty Michael E. Smith Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin Molecules cancer curcuminoid cisplatin zebrafish reactive oxygen species auditory evoked potential apoptosis cell migration |
| title | Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin |
| title_full | Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin |
| title_fullStr | Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin |
| title_full_unstemmed | Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin |
| title_short | Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin |
| title_sort | anti cancer and ototoxicity characteristics of the curcuminoids clefma and ef24 in combination with cisplatin |
| topic | cancer curcuminoid cisplatin zebrafish reactive oxygen species auditory evoked potential apoptosis cell migration |
| url | https://www.mdpi.com/1420-3049/24/21/3889 |
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