Anthracene-9, 10-dione derivatives induced apoptosis in human cervical cancer cell line (CaSki) by interfering with HPV E6 expression

  • Eur J Med Chem. 2014 Apr 22:77:334-42. doi: 10.1016/j.ejmech.2014.02.006.
Supranee Sangthong  1 ,  Naunpun Sangphech  2 ,  Tanapat Palaga  3 ,  Nattaya Ngamrojanavanich  4 ,  Songchan Puthong  5 ,  Tirayut Vilaivan  6 ,  Nongnuj Muangsin  7
Affiliations
  • 1. Program of Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • 2. Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330, Thailand.
  • 3. Department of Microbiology, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Phatumwan, Bangkok 10330, Thailand. Electronic address: [email protected].
  • 4. Biomaterials and Bioorganic Chemistry Research Group, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Phatumwan, Bangkok 10330, Thailand.
  • 5. The Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, 254 Phayathai Road, Bangkok 10330, Thailand.
  • 6. Department of Chemistry, Chulalongkorn University, 254 Phayathai Road, Bangkok 10330, Thailand.
  • 7. Biomaterials and Bioorganic Chemistry Research Group, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Phatumwan, Bangkok 10330, Thailand. Electronic address: [email protected].
PMID: 24657570 DOI: 10.1016/j.ejmech.2014.02.006
Abstract

A new series of anthracene-9, 10-dione derivatives have been synthesized to increase cytotoxic activity against human papillomavirus (HPV) positive Cancer cell line, CaSki. The highest cytotoxicity was achieved by 4-(benzylamino)-9,10-dioxo-4a,9,9a,10-tetrahydroanthracen-1-yl 4-ethylbenzenesulfonate (5) with the inhibitory concentration 50 (IC50) of 0.3 μM which is 20 times lower than that of cisplatin (CDDP; IC50 = 8.0 μM). The toxicity against non-cancerous cell line, WI-38, was low with the IC50 > 10 μM. Treatment with this compound resulted in decreasing HPV E6 expression. Furthermore, increasing p53 and decreasing Bcl-2 expression were noted. Cell cycle profiles revealed an accumulation of cells in the G2/M phase.

Keywords
10-Dione; Anthracene-9; Apoptosis; Cell cycle; Cervical cancer; HPV E6; p53.