Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer.
Antineoplastic Agents
/ administration & dosage
Caco-2 Cells
Colorectal Neoplasms
/ drug therapy
Drug Synergism
Drug Therapy, Combination
Emetine
/ administration & dosage
HT29 Cells
Humans
Mutagens
/ administration & dosage
Oxaliplatin
/ administration & dosage
Patulin
/ administration & dosage
Protein Synthesis Inhibitors
/ administration & dosage
Emetine
MTT
colorectal cancer
oxaliplatin
patulin
synergism.
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
07
2019
revised:
29
09
2019
accepted:
01
10
2019
pubmed:
19
11
2019
medline:
12
1
2021
entrez:
19
11
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31736447
pii: ACAMC-EPUB-101701
doi: 10.2174/1871520619666191021112042
doi:
Substances chimiques
Antineoplastic Agents
0
Mutagens
0
Protein Synthesis Inhibitors
0
Oxaliplatin
04ZR38536J
Patulin
95X2BV4W8R
Emetine
X8D5EPO80M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
264-273Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.