Combinatorial Use of DNA Ligase Inhibitor L189 and Temozolomide Potentiates Cell Growth Arrest in HeLa

Introduction: The issues of carcinoma drug resistance to alkylating agents such as Temozolomide (TMZ) are considered as a major concern in therapeutics. The potential ways to achieve better cancer cell growth arrest and cytotoxicity have been suggested including the combinatorial use of DNA repair protein inhibitors and genotoxic drug TMZ. Here, authors assess the ability of DNA ligase inhibitor (L189) to modulate TMZ mediated HeLa cell growth arrest and cytotoxicity. Materials and Methods: Here, authors have employed Trypan blue dye exclusion and propidium iodide (PI) using FACS to determine HeLa cell viability after exposure to TMZ with or without L189 inhibitor. Additionally, authors show the DNA ligase III protein level using ELISA and fluorescent microscopy to support the observed effects of combinatorial use of TMZ and L189. Results: In this paper, data indicate that the addition of L189 produced appreciable decrease in the growth of HeLa cells. However, combined treatment of L189 and TMZ showed enhanced TMZinduced HeLa growth arrest possibly in G2/M cell cycle phase without employing cell death mechanisms. Conclusions: These results underscore the combinatorial treatment using TMZ and L189 to bring desirable cancer cell growth arrest and future molecular study to dissect out the participating pathways.