title: Antiproliferation of HeLa cells by 3,4,5-trihydroxy-N-[2-p-tolylethyl]-benzamide is associated with induction of DNA damage and inhibition of DNA replication.
abstract: The compound 3,4,5-trihydroxy-N-[2-p-tolylethyl]-benzamide (THTEB) is one of the derivatives of tyrosol, which is p-tyrosol combined with gallic acid by an amide bond. In this study, THTEB displayed a significant antiproliferative effect on human cervical carcinoma (HeLa) cells. Cell cycle analysis revealed that THTEB could arrest HeLa cells in the S phase with a concomitant decrease in the cells' G0/G1 and G2/M phases. According to the [3H]thymidine incorporation assay results, we found that THTEB could inhibit DNA replication, which suggests that THTEB-induced S phase arrest might be the direct result of blocked DNA synthesis. However, THTEB had very weak effect on replication protein A (RPA)'s ssDNA binding activity and the topoisomerase I (topo I)-mediated DNA relaxation activity, signifying that RPA and topo I were not the main target molecules in the inhibition of DNA replication. Furthermore, by using alkaline single-cell gel electrophoresis (comet assay), we found severe DNA damage caused by THTEB. In conclusion, these results suggest that THTEB could induce tumor cell antiproliferation correlated with DNA damage and DNA replication inhibition, but the target molecule of THTEB remains elusive.
authors.affiliation: Department of Biomedicinal Chemistry and Institute of Basic Sciences, Inje University, 607 Aubang-dong, Gimhae 621-749, Republic of Korea.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Chunhui
authors.initials: C
authors.lastname: Miao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Jeong
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Son
authors.forename: Song
authors.initials: S
authors.lastname: You
authors.forename: Burm-Jong
authors.initials: BJ
authors.lastname: Lee
authors.forename: Dong-Kyoo
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001549:Benzamides / Q000138:chemical synthesis / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity; D051716:Replication Protein A / Q000378:metabolism; D016196:S Phase / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004273:DNA, Neoplasm; C497167:RPA1 protein, human; D051716:Replication Protein A; D005707:Gallic Acid; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D010626:Phenylethyl Alcohol