Premium
Curcumin enhances dasatinib‐induced inhibition of growth and transformation of colon cancer cells
Author(s) -
Nautiyal Jyoti,
Banerjee Sanjeev,
Kanwar Shailender S.,
Yu Yingjie,
Patel Bhaumik B,
Sarkar Fazlul H.,
Majumdar Adhip P.N.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25410
Subject(s) - dasatinib , colorectal cancer , cancer research , curcumin , medicine , cancer , proto oncogene tyrosine protein kinase src , cancer cell , pharmacology , receptor , myeloid leukemia , imatinib
Colorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF‐1R as well as c‐Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS‐354825; Bristol‐Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a nontoxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter, we utilized C57BL/6 APC Min +/− mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: ( i ) colony formation, ( ii ) invasion through extracellular matrix and ( iii ) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT‐116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in Apc Min +/− mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer.