Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Dose Dependent Synergism from Combination of Platinum Drugs with Curcumin against Colorectal Cancer Cell Lines

Hana Bali1, Jun Qing Yu1, Philip Beale2, and Fazlul Huq3

+ Author Affiliations

Journal of Angiotherapy 4(1) 176-193 https://doi.org/10.25163/angiotherapy.41210611810120920

Submitted: 18 August 2020  Revised: 04 September 2020  Published: 12 September 2020 

Abstract

Introduction: Colorectal cancer is the fourth most common cause of cancer mortality. More than 41265 new cases of colorectal cancer were detected and around 15903 colorectal cancer deaths occurred in year 2014 worldwide according to the statistical study from the cancer research. Chemotherapy is still in the main stream of the management of colorectal cancer along with surgery and radiotherapy. Aim: The objective of the present study was to investigate the activity of curcumin in combination with platinum drugs against colorectal cancer models (HT-29, Caco-2, LIM-1215 and LIM-2405). Methods: IC50 values of cisplatin (Cs) , oxaliplatin (Ox), and curcumin (Cur) were determined against four human colorectal cancer cell lines using MTT reduction assay. Combined drug activity was determined as a factor of sequence of administration (0/0, 0/4 and 4/0 h) and added concentrations.  DNA binding and proteomics were carried out to obtain insight into molecular mechanisms of drug action. Results: Oxaliplatin in combination with curcumin produced strong synergism in the tested cell lines. Cellular accumulation study, platinum-DNA binding study and DNA damage study revealed the mechanism of combined drug affects. Upregulation of K1C18, GRP78, IDHC and Cofilin-1 proteins was considered to be associated with the synergistic combined effects of oxaliplatin with curcumin. Conclusion: Ox in combination Cur demonstrated very high synergism against HT-29 and Caco-2 cell lines. Synergism from Ox with Cur may beassociated with greater platinum-DNA binding. Proteomics revealed that the elevated expressions of K1C18, GRP78, IDHC and Cofilin1 may be responsible for the synergistic activity obtained from the combination of Ox with Cur.

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