Molecular Characterization of Propolis-Induced Cell Death in Saccharomyces cerevisiae

Abstract

Propolis, a natural product of plant resins, is used by the bees to seal holes in their honeycombs and protect the hive entrance. However, propolis has also been used in folk medicine for centuries. Here, we apply the power of Saccharomyces cerevisiae as a model organism for studies of genetics, cell biology, and genomics to determine how propolis affects fungi at the cellular level. Propolis is able to induce an apoptosis cell death response. However, increased exposure to propolis provides a corresponding increase in the necrosis response. We showed that cytochrome c but not endonuclease G (Nuc1p) is involved in propolis-mediated cell death in S. cerevisiae. We also observed that the metacaspase YCA1 gene is important for propolis-mediated cell death. To elucidate the gene functions that may be required for propolis sensitivity in eukaryotes, the full collection of about 4,800 haploid S. cerevisiae deletion strains was screened for propolis sensitivity. We were able to identify 138 deletion strains that have different degrees of propolis sensitivity compared to the corresponding wild-type strains. Systems biology revealed enrichment for genes involved in the mitochondrial electron transport chain, vacuolar acidification, negative regulation of transcription from RNA polymerase II promoter, regulation of macroautophagy associated with protein targeting to vacuoles, and cellular response to starvation. Validation studies indicated that propolis sensitivity is dependent on the mitochondrial function and that vacuolar acidification and autophagy are important for yeast cell death caused by propolis.

Farnesol-induced cell death in the filamentous fungus Aspergillus nidulans

“…There is a low nucA mRNA accumulation when A. nidulans germlings were exposed to oxidative stressing agents, such as H 2 O 2 and paraquat and DNA-damaging agents [hydroxyurea, MMS (methyl methanesulfonate) and bleomycin]. The nucA deletion strain has no apparent growth or conidiation defects and did not show increased susceptibility to FOH and we were not able to observe any other phenotype of susceptibility to several agents that cause cell death [36]. However, the nucA deletion mutant is more sensitive to 4-NQO (4-nitroquinoline oxide), and its quiescent and germinating conidia are slightly more sensitive to UV light.…”

“…The same results were observed when NucA::mRFP was exposed to different concentrations of 4-NQO. Cell fractionation studies showed that NucA::mRFP localizes to the mitochondria when NucA::mRFP germlings were exposed or not to FOH [36]. These results indicate that NucA is genetically interacting with these two genes aiming to repair DNA damage caused by these genotoxins.…”

“…Upon apoptosis induction, translocation of mammalian EndoG and its S. cerevisiae homologue NUC1 to the nucleus coincides with large-scale DNA fragmentation [33][34][35]. Recently, we described a homologue of EndoG in the filamentous fungi by investigating if the A. nidulans EndoG homologue, named nucA ENDOG , is being activated during FOH-induced cell death [36]. There is a low nucA mRNA accumulation when A. nidulans germlings were exposed to oxidative stressing agents, such as H 2 O 2 and paraquat and DNA-damaging agents [hydroxyurea, MMS (methyl methanesulfonate) and bleomycin].…”

Elementery Analysis and anti-Tumor Activity on Glioblastoma Cell Lines of Propolis Samples from Giresun Province of Turkey

“…Geographical molecular marker is also important for analyzing the location of propolis taken [10]. The composition of propolis is dependent on the flora, season, and time of the collection [20].…”

“…The identity and the mechanism of action of the chemical compounds present in the propolis are investigated [9]. To identify the cellular targets of any bioactive compounds is a very difficult task [10][11][12].…”