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

Norlaily Mohd Ali, Swee Keong Yeap, Nadiah Abu, Kian Lam Lim, Huynh Ky, Ahmad Zaim Mat Pauzi, Wan Yong Ho, Sheau Wei Tan, Han Kiat Alan-Ong, Seema Zareen, Noorjahan Banu Alitheen, M. Nadeem Akhtar

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number30
JournalCancer Cell International
Volume17
Issue number1
DOIs
Publication statusPublished - 21 Feb 2017

Fingerprint

Curcumin
MCF-7 Cells
Apoptosis
Breast Neoplasms
Cell Cycle
G2 Phase
Cell Division
Flow Cytometry
Curcuma
Rhizome
Caspase 9
Caspases
Cell Cycle Checkpoints
Cytochromes c
Biological Availability
Glutathione
Real-Time Polymerase Chain Reaction
Reactive Oxygen Species
Oxidative Stress
Up-Regulation

Keywords

  • Apoptosis
  • CDC2 phosphorylation
  • Cell cycle arrest
  • DK1
  • ROS

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells. / Ali, Norlaily Mohd; Yeap, Swee Keong; Abu, Nadiah; Lim, Kian Lam; Ky, Huynh; Pauzi, Ahmad Zaim Mat; Ho, Wan Yong; Tan, Sheau Wei; Alan-Ong, Han Kiat; Zareen, Seema; Alitheen, Noorjahan Banu; Akhtar, M. Nadeem.

In: Cancer Cell International, Vol. 17, No. 1, 30, 21.02.2017.

Research output: Contribution to journalArticle

Ali, Norlaily Mohd ; Yeap, Swee Keong ; Abu, Nadiah ; Lim, Kian Lam ; Ky, Huynh ; Pauzi, Ahmad Zaim Mat ; Ho, Wan Yong ; Tan, Sheau Wei ; Alan-Ong, Han Kiat ; Zareen, Seema ; Alitheen, Noorjahan Banu ; Akhtar, M. Nadeem. / Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells. In: Cancer Cell International. 2017 ; Vol. 17, No. 1.
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AU - Lim, Kian Lam

AU - Ky, Huynh

AU - Pauzi, Ahmad Zaim Mat

AU - Ho, Wan Yong

AU - Tan, Sheau Wei

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