A novel bispidinone analog induces S-phase cell cycle arrest and apoptosis in HeLa human cervical carcinoma cells

Abstract

2,4,6,8-(3)-Tetranitrophenyl-3,7-diazabicyclo[3.3.1]nonan-9-one (B16), a bispidinone analog, was synthesized to investigate its effects on cell viability, the cell cycle, and apoptotic pathways in HeLa human cervical cancer cells. B16 decreased the percentage of viable cells in WST-8 assays, and morphological changes associated with apoptotic cell death were observed, including cell shrinkage and disruption. Annexin V-FITC/PI dual staining assays showed that B16 significantly increased the early apoptosis of HeLa cells after 24 h of treatment. Moreover, DNA content analysis and [3H]-thymidine incorporation assays showed that B16 induced S-phase cell cycle arrest and inhibited DNA replication after 24 h of treatment. Following treatment with 25 µM of B16, an increase in reactive oxygen species and a decrease in mitochondrial membrane potential were observed by flow cytometry. In addition, the expression levels of caspase cascade and Bcl-2 family proteins determined by western blotting suggested that the induction of apoptosis by B16 was associated with a caspase- and mitochondrial-dependent pathway in HeLa cells. In conclusion, B16 induced early apoptosis and S-phase cell cycle arrest in HeLa cells via a caspase- and mitochondrial‑dependent pathway.

The Bispidinone Derivative 3,7-Bis-[2-(S)-amino-3-(1H-indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one Dihydrochloride Induces an Apoptosis-Mediated Cytotoxic Effect on Pancreatic Cancer Cells In Vitro

“…These results agree with two recent studies investigating the cytotoxic effect of bispidinone analogues on HeLa cervical cancer cells in vitro [22,23]. Both studies reported significant apoptosis-mediated cytotoxicity from two bispidinone analogues: 2,4,6,8-tetrakis(2-methoxyphenyl)-3,7-diazabicyclo[3.3.1]nonan-9-one [22] and 2,4,6,8-(3)-tetranitrophenyl-3,7-diazabicyclo[3.3.1]nonan-9-one [23]. Together, these results emphasize how apoptotic events can have a different time course depending on the concentration of the cytotoxic agent.…”

“…Due to the known complexity and heterogeneity of pancreatic cancer [28,29,30], there are potentially significant benefits in the continued discovery of novel targeted drug treatments. Recent research has shown that tetraaryl functionalised bispidinone analogues induce apoptosis in HeLa cervical cancer cell lines [22,23]. However, no studies to date have assessed the potential effects of aliphatic and aromatic N , N -disubstituted bispidinone derivatives on PC cell lines.…”

“…In contrast to bispidines, few studies investigating the biological properties of bispidinone derivatives and their potential biological effects, in particular regarding anti-cancer activity have to date been undertaken [22,23]. In these cases, considerable variation in substituent attachment and pattern exists making further study of the system essential to develop a more comprehensive understanding of structure-activity relationships.…”

Radiation‐Sensitive Dendrimer‐Based Drug Delivery System

“…Radiation energy is deposited in cell nuclei, elicits mutagenic or clastogenic effects, and causes damage 57. We confirmed dendrimer carrier uptake by HeLa cells and observed significant drug presence in the nucleus ( Figure 5 ).…”

Aptamer-Functionalized Drug Nanocarrier Improves Hepatocellular Carcinoma toward Normal by Targeting Neoplastic Hepatocytes

“…Results of cell cycle analysis revealed that different experimental formulations caused cell arrest at the G 2 /M and S phases, leading to the activation of three principal checkpoints of cell cycle, namely, G 1 /S, G 2 /M, and spindle assembly checkpoints at metaphase/anaphase transitions (Figures 1A and 1B). 22,23 The maximum degree of cell arrest was observed in both types of cancer cells upon their treatment with PTX-NPL5. The comparative differentiation between the different investigated formulations to produce arrest of cells at the different phases of the cell cycle is provided in Figures 1A and 1B.…”