Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer

Author:

Alam Md. Nur1ORCID,Yu Jun Q.1,Beale Philip2,Huq Fazlul1

Affiliation:

1. Discipline of Pathology, Sydney Medical School, A26-RC Mills Room 105, University of Sydney, Sydney, NSW, Australia

2. Sydney Cancer Centre, Concord Hospital, Sydney, NSW 2139, Australia

Abstract

Background: Colorectal cancer is the third most commonly diagnosed cancer in the world, causing many deaths every year. Combined chemotherapy has opened a new horizon in treating colorectal cancer. The objective of the present study is to investigate the activity of oxaliplatin in combination with emetine and patulin against colorectal cancer models. Methods: IC50 values of oxaliplatin, emetine and patulin were determined against human colorectal cancer cell lines (HT-29 and Caco-2) using MTT reduction assay. Synergistic, antagonistic and additive effects from the selected binary combinations were determined as a factor of sequence of administration and added concentrations. Proteomics was carried out to identify the proteins which were accountable for combined drug action applying to the selected drug combination. Results: Oxaliplatin in combination with patulin produced synergism against human colorectal cancer models depending on dose and sequence of drug administration. Bolus administration of oxaliplatin with patulin proved to be the best in terms of synergistic outcome. Altered expressions of nine proteins (ACTG, PROF1, PPIA, PDIA3, COF1, GSTP1, ALDOA, TBA1C and TBB5) were considered for combined drug actions of oxaliplatin with patulin. Conclusion: Bolus administration of oxaliplatin with patulin has the potential to be used in the treatment of colorectal cancer, and would warrant further evaluation using suitable animal model.

Publisher

Bentham Science Publishers Ltd.

Subject

Cancer Research,Pharmacology,Molecular Medicine

Reference65 articles.

1. Alam M.N.; Almoyad M.; Huq F.; Polyphenols in colorectal cancer: Current state of knowledge including clinical trials and molecular mechanism of action. BioMed Res Int 2018,2018

2. Schinzari G.; Rossi E.; Mambella G.; Strippoli A.; Cangiano R.; Mutignani M.; Basso M.; Cassano A.; Barone C.; First-line treatment of advanced biliary ducts carcinoma: A randomized Phase II study evaluating 5-FU/LV plus oxaliplatin (Folfox 4) Versus 5-FU/LV (de Gramont Regimen). Anticancer Res 2017,37(9),5193-5197

3. Muhammad N.; Steele R.; Isbell T.S.; Philips N.; Ray R.B.; Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death. Oncotarget 2017,8(39),66226-66236

4. Mohammad N.; Singh S.V.; Malvi P.; Chaube B.; Athavale D.; Vanuopadath M.; Nair S.S.; Nair B.; Bhat M.K.; Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex. Sci Rep 2015,5,11853

5. Nessa M.U.; Beale P.; Chan C.; Yu J.Q.; Huq F.; Synergism from combinations of cisplatin and oxaliplatin with quercetin and thymoquinone in human ovarian tumour models. Anticancer Res 2011,31(11),3789-3797

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