Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells

• Main Authors: Mohd Ali, Norlaily, Swee, Keong Yeap, Abu, Nadiah, Kian, Lam Lim, Ky, Huynh, Pauzi, Ahmad Zaim Mat, Wan, Yong Ho, Sheau, Wei Tan, Alan‑Ong, Han Kiat, Zareen, Seema, Alitheen, Noorjahan Banu, Akhtar, M. Nadeem
• Format: Article
• Language: English
• Published: BioMed Central 2017
• Online Access: http://psasir.upm.edu.my/id/eprint/63373/1/Synthetic%20curcumin%20derivative%20DK1%20possessed%20G2M%20arrest%20and%20induced%20apoptosis%20through%20accumulation%20of%20intracellular%20ROS%20in%20MCF-7%20breast%20cancer%20cells.pdf; http://psasir.upm.edu.my/id/eprint/63373/

Aims: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability. Main methods: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels. Key findings: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9. Significance: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.