Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Sequenced Combinations of Cisplatin and Selected Phytochemicals Towards Overcoming Drug Resistance in Ovarian Tumour Models

Version 1 : Received: 28 August 2020 / Approved: 30 August 2020 / Online: 30 August 2020 (12:06:32 CEST)

A peer-reviewed article of this Preprint also exists.

Althurwi, S.I.; Yu, J.Q.; Beale, P.; Huq, F. Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models. Int. J. Mol. Sci. 2020, 21, 7500. Althurwi, S.I.; Yu, J.Q.; Beale, P.; Huq, F. Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models. Int. J. Mol. Sci. 2020, 21, 7500.

Journal reference: Int. J. Mol. Sci. 2020, 21, 7500
DOI: 10.3390/ijms21207500

Abstract

Background: In the present study, cisplatin, artemisinin and oleanolic acid were evaluated alone and in combination, on human ovarian A2780, A2780ZD0473R and A2780cisR cancer cell lines with aim of overcoming cisplatin resistance and side effects. Methods: Cytotoxicity was assessed by MTT reduction assay. CI values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Results: Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism and biosynthetic processes and drug resistance and detoxification. Conclusion: Results indicate that appropriately sequenced combinations of cisplatin with ART and OA may provide a means to reduce side effects and circumvent platinum resistance.

Subject Areas

Ovarian cancer; drug resistance; apoptosis; proteomics; combination; cytotoxicity; artemisinin; oleanolic acid; platinum drugs; cisplatin

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.