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

Supranee Sangthong; Naunpun Sangphech; Tanapat Palaga; Nattaya Ngamrojanavanich; Songchan Puthong; Tirayut Vilaivan; Nongnuj Muangsin

doi:10.1016/j.ejmech.2014.02.006

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. Epub 2014 Feb 27.

Authors

Supranee Sangthong¹, Naunpun Sangphech², Tanapat Palaga³, Nattaya Ngamrojanavanich⁴, Songchan Puthong⁵, Tirayut Vilaivan⁶, Nongnuj Muangsin⁷

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: Tanapat.p@chula.ac.th.
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: Nongnuj.j@chula.ac.th.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthraquinones / chemical synthesis
Anthraquinones / chemistry
Anthraquinones / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Oncogene Proteins, Viral / biosynthesis*
Oncogene Proteins, Viral / deficiency
Oncogene Proteins, Viral / genetics
Repressor Proteins / biosynthesis*
Repressor Proteins / deficiency
Repressor Proteins / genetics
Structure-Activity Relationship

Substances

Anthraquinones
Antineoplastic Agents
E6 protein, Human papillomavirus type 16
Oncogene Proteins, Viral
Repressor Proteins
9,10-anthraquinone