Cisplatin is an anticancer drug that can induce apoptosis. In this study, we investigated the effect of mitochondrial DNA (mtDNA) depletion on cisplatin-induced cell death using a human osteosarcoma cell line (143B) and mtDNA-depleted 143B cells (143B-rho0). Results showed that cisplatin decreased cell survival in 143B-rho0 cells. Moreover, cisplatin induced a greater extent of apoptosis-associated DNA fragmentation and caspase 3 activation in 143B-rho0 cells. The release of mitochondrial cytochrome c into cytosol by cisplatin was enhanced more obviously in 143B cells than in 143B-rho0 cells; however, in the control group of 143B-rho0 cells, it was already dramatically greater. Depletion of mtDNA may increase sensitivity of cells to cisplatin-induced apoptosis by enhancing caspase 3 activation via both cytochrome c-dependent and -independent pathways.

Estrogen and progestins have adverse effects, and many of these adverse effects are caused by progestins. Due to this, many women choose to use botanical alternatives for hormone replacement therapy, which does not trigger steroidogenic properties. Therefore, it is necessary to screen these herbs for progestogenic and anti-progestogenic properties. Extract of 13 Chinese medicinal plants were analysed for progestogenic and anti-progestogenic activities by using progesterone response element-driven luciferase reporter gene bioassay. MTT assay was carried out to investigate the cytotoxic effect of herb extract on PAE cells. Among the 13 herbs, Dipsacus asperoides extract exhibited progestogenic activity, and 10 species - Cortex eucommiae, Folium artemisiae argyi, Glycyrrhiza uralensis, Angelica sinensis, Atractylodes macrocephala koidz, Scutellaria baicalensis, Cuscuta chinensis, Euscaphis japonica, Ailanthus altissima, and Dioscorea opposita - were recognized to have anti-progestogenic like activities. Extract of Dipsacus asperoides demonstrated dose-dependent progestogenic activity, and the progestogenic activity of 100 (mu)g/mL extracts was equivalent to 31.45 ng/mL progesterone activity. Herbs extracts that exhibited anti-progestogenic-like activity also inhibited the 314.46 ng/mL progesterone activity in a dose-response manner. None of the herb extracts shown significant toxic effect on PAE cells at 40-100 (mu)g/mL compared to control. This discovery will aid selection of suitable herbs for hormone replacement therapy.

Non-homologous end joining (NHEJ) is one of the major mechanisms for rejoining of DNA double-strand breaks. Knowledge of the molecular mechanism of NHEJ will help us to understand how this process preserves genome integrity, and how NHEJ errors cause chromosomal rearrangements that lead to cancer. Several critical participants in the NHEJ pathway have been identified and some mechanistic steps have been characterized. At present, a significant gap in our understanding of NHEJ is how NHEJ factors assemble at DSBs. It is plausible that additional, as yet unidentified, factors contribute to NHEJ assembly. We have biochemical and biological data implicating a short open reading frame (sORF)-encoded protein in NHEJ. sORFs are found in all genomes. Ribosome profiling, mass spectroscopy and RNA sequencing have predicted the existence of numerous sORF-encoded proteins of <100 amino acids in size. While the functional significance of the majority of these small proteins is not clear, we recently discovered that a 69 amino acid protein encoded by chromosome 7 open-reading frame 49 (C7orf49) interacts with critical NHEJ factors in human cells, and stimulates NHEJ in cell-free extracts. Treatment of cells with the DSB-inducing agent etoposide increased C7orf49 expression and nuclear localization, and knockdown of C7orf49 sensitized cells to etoposide. C7orf49-deficient cells exhibited a mild proliferation defect and increased sensitivity to etoposide. Our data suggest that this small protein may play an important role in double-strand beak repair by NHEJ and highlights the potential biological relevance of sORF-encoded proteins in the DNA damage response and in DNA repair. Citation Format: Les Hanakahi, Matthew Summerlin, Yi-Chia Tang, Jinho Heo. Does a short open reading frame (sORF)-encoded protein participate in DNA repair. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2760.