No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields

The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa–FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 μm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell–cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa–FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics.

Osthole Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Cervical Carcinoma HeLa Cells

Purpose. To study the effect of osthole extract on proliferation, migration, invasion, and apoptosis of human cervical carcinoma HeLa cells and investigate its underlying mechanism. Methods. HeLa cells were exposed to osthole at various concentrations. Cell viability, migration, and invasion were detected by MTT assay, scratch wound-healing assay, and invasion assay, respectively. The proportion of cells undergoing apoptosis was analyzed by flow cytometry. Western blot and RT-qPCR were performed to determine changes in the expression of key factors in the Wnt/β-catenin signaling pathway. Results. The osthole extract effectively inhibited the proliferation, migration, and invasion potential of HeLa cells in a dose-dependent manner. The rate of apoptosis induction in HeLa cells treated with the osthole extract for 48 h was significantly higher than that of the untreated controls. Outcomes of the western blotting analysis and RT-qPCR showed that the expression of β-catenin, c-Myc, cyclin D1, survivin, and MMP-9 was significantly inhibited. Conclusion. Osthole could significantly inhibit the malignant behavior of HeLa cells and induce cellular apoptosis. Inactivation of the Wnt/β-catenin signaling pathway by osthole may be a mechanism to control cancer metastasis.

Antiapoptotic activity of methyl (3R,4E,6Z,15E)-3-hydroxyoctadecatrienoate in human cervical carcinoma HeLa cells

ABSTRACT Inhibitors of thapsigargin-induced cell death in human cervical carcinoma HeLa cells were screened among the metabolites of marine organisms. The MeOH extract of the cyanobacterium Rivularia sp. was found to exhibit inhibitory activity. Column chromatography purification was used to isolate methyl (3R,4E,6Z,15E)-3-hydroxyoctadecatrienoate (MHO) as the active compound. MHO was determined to inhibit apoptotic stimuli-induced cell death in HeLa cells.

Synthesis of the 6-Substituted Imidazo[1,2-a]Pyridine-3-yl-2- Phosphonopropionic Acids as Potential Inhibitors of Rab Geranylgeranyl Transferase

Twelve phosphonopropionates derived from 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid (3-IPEHPC) were synthesized and evaluated for their activity as inhibitors of protein geranylgeranylation. The nature of the substituent in the C6 position of imidazo[1,2-a]pyridine ring was responsible for the compound's activity against Rab geranylgeranyl transferase (RGGT). The most active inhibitors disrupted Rab11A prenylation in the human cervical carcinoma HeLa cell line. The esterification of carboxylic acid in the phosphonopropionate moiety turned the inhibitor into an inactive analog.

Comparative Cytotoxic Activity of Wild Harvested Stems and In Vitro-Raised Protocorms of Dendrobium chryseum Rolfe in Human Cervical Carcinoma and Glioblastoma Cell Lines

From the medicinal orchid Dendrobium chryseum Rolfe, which is used in traditional and folk Chinese medicine, the protocorms were raised in Murashige and Skoog (MS) media in three strengths, full strength (FMS), half strength (1/2 MS), and quarter strength (1/4 MS), with or without the phytohormones 6-benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) and coconut water (CW). The comparative cytotoxic activities of the wild and in vitro-raised protocorms were evaluated in human cervical carcinoma (HeLa) and human glioblastoma (U251) cell lines by MTT assay. In in vivo and in vitro, the methanol extracts of D. chryseum showed significant cytotoxic activities. Significant growth inhibition (%) and potent IC50 values were demonstrated in HeLa cell lines (49.79% (210.5 μg/mL) for in vitro-raised Dendrobium chryseum (DCT) versus 46.97% (226.5 μg/mL) for wild Dendrobium chryseum (DCW)). Similarly, activities against U251 cell lines exhibited also significant inhibition (28.76% (612.54 μg/mL) for DCW and 17.15% (1059.92 μg/mL) for DCT). The cytotoxic activities of both, wild and tissue-cultured samples, were superior in HeLa cells. In U251 cells, the wild sample was more active than the tissue-cultured one with a moderate cytotoxic effect. Hence, protocorm culture may therefore be a promising future tool for producing pharmacologically bioactive compounds in medicinal orchids. Such sustainable technology approach will minimize the pressure on the natural population of threatened but commercially important medicinal orchids.

Apoptosis induction by α-mangostin-loaded nanoparticles in human cervical carcinoma cells

The compound α-mangostin (AMG) extracted from Garcinia mangostana L. has potent anticancer properties but its clinical application is limited because of its poor solubility. In this study, AMG-loaded nanoparticles (NMG) were synthesized using a new formula and their apoptosis activity against human cervical carcinoma (HeLa) cells was investigated in comparison with organic solvent-soluble AMG in free form. The NMG was successfully synthesized with a particle size of <50 nm, polydispersity index <0.3, and zeta potential of −35.2 mV. At a concentration of 10 μg/mL, AMG reduced cell survival by 60%, whereas NMG treatment resulted in >90% cell death (p < 0.05). The AMG- or NMG-treated cells also showed changes in the size and shape and exhibited enhanced intensity of blue-stained nuclei, as well as decreased cell density, especially in NMG-treated cells. After 24 h of incubation with AMG or NMG, the cells went through late apoptosis at a rate of approximately 34% in 20 μg/mL AMG treatment and 27% in 10 μg/mL NMG treatment (p < 0.05). Thus, HeLa cells underwent more pronounced cell death through apoptosis induction caused by the NMG treatment compared to that caused by AMG. Clearly, the new NMG improved AMG bioavailability while maintaining the desired activity.