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Mol Cell Biochem (2011) 354:247252 DOI 10.1007/s11010-011-0824-3
Curcumin induces DNA damage and caffeine-insensitive cell cycle arrest in colorectal carcinoma HCT116 cells
Jin-Jian Lu Yu-Jun Cai Jian Ding
Received: 19 January 2011 / Accepted: 15 April 2011 / Published online: 28 April 2011 Springer Science+Business Media, LLC. 2011
Abstract Curcumin (CUR), a polyphenol derived from the plant Curcuma longa, displays potential anti-cancer activity. One of the mechanisms stems from its ability to elicit cell cycle arrest followed by suppression of cell proliferation. Herein, we reported that CUR signicantly induced DNA damage and mediated S and G2/M phase arrest in colorectal carcinoma HCT116 cells. Unlike etoposide, a classical topoisomerase II inhibitor, CUR-triggered G2/M phase arrest was hardly reversed by caffeine (CAFF) which is an inhibitor of activated ataxia-telangiectasia-mutated (ATM)/ ATM- and Rad3-related (ATR), indicating that ATM and ATR signaling pathways may be not involved in CUR-mediated S and G2/M phase arrest in HCT116 cells. Furthermore, we demonstrated that CUR caused mitosis arrest in HCT116 cells by using mitotic protein monoclonal antibody-2 as a mitosis marker and the surface plasmon resonance assay. The ndings provide new mechanisms of cell proliferation inhibition triggered by CUR in HCT116 cells.
Keywords Curcumin DNA damage Caffeine
S phase arrest Mitosis arrest Tubulin
AbbreviationAPH AphidicolinATM Ataxia-telangiectasia-mutated ATR ATM- and Rad3-related CAFF CaffeineCUR CurcuminNOC NocodazoleVP16 Etoposide
Introduction
Curcumin (CUR), the major yellow-colored dietary pigment from the plant Curcuma longa, has long been used as a dietary spice in several countries [1]. Its chemoprevention and chemotherapy activities have been extensively studied and it is currently used in clinical trials [13]. CUR exerts its anti-cancer activity through inhibiting cell proliferation, invasion, angiogenesis, and metastasis in different cancers via interaction with multiple cellular signaling molecules [15]. It also triggers cell cycle arrest in different tumor cell types, indicating multiple mechanisms are involved in these events [69].
Recent studies demonstrated that CUR elicits DNA damage [1012], which is one of the molecular events associated with cell cycle arrest. In general, cellular responses to DNA damage are primarily coordinated by two distinct kinases, ataxia-telangiectasia-mutated (ATM)/ ATM- and Rad3-related (ATR), which further lead to cell cycle arrest or apoptosis [13, 14]. Herein, we found that CUR induced DNA damage, S and G2/M phase arrest in the colorectal carcinoma HCT116 cells....