- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Synthesis of water soluble silicon phthacyanine, naphthalocyanine bearing pyridine groups and investigation of their DNA interaction, topoisomerase inhibition, cytotoxic effects and cell cycle arrest properties
摘要： In this work, axially [3,5-bis(3-pyridin-4-ylpropoxy)phenyl]methoxy groups substituted silicon (IV) phthalocyanine 2, napthalocyanine 3 and their water soluble derivatives 2a, 3a were synthesized and DNA interaction, topoisomerases inhibitory properties, cytotoxicity against five carcinoma cell lines of water soluble derivatives were examined. The calf thymus DNA (CT-DNA) binding properties of 2a and 3a were monitored using UV-Vis spectroscopy and agarose gel electrophoresis. The results showed that the compounds interacted to CT-DNA via intercalation with Kb values of 3.94 ± (0.15) ×106 and 1.08 ± (0.10) ×105 M-1. In DNA cleavage studies, the compounds cleaved to supercoiled pBR322 plasmid DNA significantly with irradiation as compared to without irradiation. The results of topoisomerases studies claimed that both compounds had inhibitory effects against topoisomerases. In the cytotoxicity studies, the CC50 values of the compounds were found in range of 2.15-52.97 μM against to five carcinoma cell lines. The SI values of 3a were found as 4.51, 1.43 and 3.66 against A549, BT20 and SK-MEL 128 cell lines. The cell cycle arrest was investigated against A549 cells by flow cytometry and obtained results indicated that both compounds induce cell cycle arrest at G0/G1 phase. All of obtained results demonstrated that 3a had lead anticancer agent toward lung, breast and melanoma due to its high selectivity to cancer cell lines.
关键词： Water solubility,Cytotoxicity,Topoisomerases.,DNA,Phthalocyanine,Cell cycle arrest
更新于2025-09-19 17:15:36
-
Brahma deficiency in keratinocytes promotes UV carcinogenesis by accelerating the escape from cell cycle arrest and the formation of DNA photolesions
摘要： Background: Ultraviolet radiation (UVR) is the principal cause of keratinocyte skin cancers. Previous work found that levels of the chromatin remodelling protein, Brahma (Brm), are diminished during the progression from actinic keratoses to cutaneous squamous cell carcinomas in humans, and its loss in UV-irradiated mouse skin causes epidermal hyperplasia and increased tumour incidence. Methods: The skins of mice and mouse and human keratinocytes deficient in Brm were exposed to UVR and evaluated for cell cycle progression and DNA damage response. Objective: To identify the mechanisms by which loss of Brm contributes to UVR-induced skin carcinogenesis. Results: In both mouse keratinocytes and HaCaT cells, Brm deficiency led to an increased cell population growth following UVR exposure compared to cells with normal levels of Brm. Cell cycle analysis using a novel assay showed that Brm-deficient keratinocytes entered cell cycle arrest normally, but escaped from cell cycle arrest faster, enabling them to begin proliferating earlier. In mouse keratinocytes, Brm primarily affected accumulation in G0/G1-phase, whereas in HaCaT cells, which lack normal p53, accumulation in G2/M-phase was affected. Brm-deficient keratinocytes in mouse skin and human cell cultures also had higher levels of UVR-induced cyclobutane pyrimidine dimer photolesions. These effects occurred without any compensatory increase in DNA repair or cell death to remove photolesions or the cells that harbor them from the keratinocyte population. Conclusion: The loss of Brm in keratinocytes exposed to UVR enables them to resume proliferation while harboring DNA photolesions, leading to an increased fixation of mutations and, consequently, increased carcinogenesis.
关键词： SWI/SNF,Cutaneous squamous cell carcinoma,UV radiation,Cell cycle arrest,DNA damage
更新于2025-09-04 15:30:14