Synthesis of an anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell line.
Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2- carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel-Crafts condensation reaction. The mechanisms of cytotoxicity of DHAQC (2) in human breast cancer MCF-7 cells were further investigated. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DHAQC (2) exhibited potential cytotoxicity and selectivity in the MCF-7 cell line, comparable with the naturally occurring anthraquinone damnacanthal. DHAQC (2) showed a slightly higher IC50 (inhibitory concentration with 50% cell viability) value in the MCF-7 cell line compared to damnacanthal, but it is more selective in terms of the ratio of IC50 on MCF-7 cells and normal MCF-10A cells. (selective index for DHAQC (2) was 2.3 and 1.7 for damnacanthal). The flow cytometry cell cycle analysis on the MCF-7 cell line treated with the IC50 dose of DHAQC (2) for 48 hours showed that DHAQC (2) arrested MCF-7 cell line at the G2/M phase in association with an inhibited expression of PLK1 genes. Western blot analysis also indicated that the DHAQC (2) increased BAX, p53, and cytochrome c levels in MCF-7 cells, which subsequently activated apoptosis as observed in annexin V/propidium iodide and cell cycle analyses. These results indicate that DHAQC (2) is a synthetic, cytotoxic, and selective anthraquinone, which is less toxic than the natural product damnacanthal, and which demonstrates potential in the induction of apoptosis in the breast cancer MCF-7 cell line.
Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia.
SweeKeong
S
Yeap
Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia.
Muhammad Nadeem
MN
Akhtar
Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor Darul Ehsan, Malaysia.
Kian Lam
KL
Lim
Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia ; Bright Sparks Unit, University of Malaya, Kuala Lumpur, Malaysia.
Nadiah
N
Abu
School of Biomedical Sciences, University of Nottingham Malaysia Campus, Selangor Darul Ehsan, Malaysia.
Wan Yong
WY
Ho
Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia.
Seema
S
Zareen
Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia.
Kiarash
K
Roohani
Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia.
Huynh
H
Ky
Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia.
Sheau Wei
SW
Tan
Scientific Chairs Unit, Taibah University, Medina, Saudi Arabia.
Nordin
N
Lajis
Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia ; Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia.
Noorjahan Banu
NB
Alitheen
D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C000609613:1,3-dihydroxy-9,10-anthraquinone-2-carboxylic acid; D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic
cell cycle; cytotoxic; selective index