Inhibition of Saccharomyces cerevisiae Pdr5p by a natural compound extracted from Brazilian Red Propolis

Abstract

Multidrug resistance of cancer cells and pathogenic microorganisms leading to the treatment failure of some forms of cancer or life-threatening bacterial or fungal infections is often caused by the overexpression of multidrug efflux pumps belonging to the ATP-binding cassette transporters superfamily. The multidrug resistance of fungal cells often involves the overexpression of efflux pumps belonging to the pleiotropic drug resistance (PDR) family of ABC transporters. Possibly the best-studied fungal PDR transporter is the multidrug resistance transporter Pdr5p of Saccharomyces cerevisiae. Some research groups have been searching for new inhibitors of these efflux pumps in order to alleviate resistance. Natural products are a great source for the discovery of new compounds with biological activity. Propolis is a complex resinous material collected by honeybees from exudates and buds of certain plant sources and this material is thought to serve as a defense substance for bee hives. Propolis is widely used in traditional medicine and is reported to have a broad spectrum of pharmacological properties. Literature reported some biological functionalities of propolis, such as antibacterial, antiviral, fungicidal, antiinflammatory and anti-carcinogenic activities. The chemical composition of propolis is qualitatively and quantitatively variable. Components isolated from methanolic extract of red Brazilian propolis (Alagoas, Northeast of Brazil) are isoflavonoids (including pterocarpans, isoflavans, isoflavones), flavanones and polyprenylated benzophenones. In this work we demonstrated the effects of five different isolated compounds on the ATPase activity of Pdr5p. Out of all five substances tested, only BRP-1 was able to completely abolish the enzymatic activity while others worked as positive modulators of the enzyme activity. BRP-1also inhibited the efflux of Rhodamine 6G from yeast cells overexpressing Pdr5p. Taken together, these results demonstrate that Brazilian propolis could be a source of promising compounds that can alleviate the MDR phenomenon, particularly in some fungi, where it could be used as an adjuvant for the treatment with azoles.

Antimicrobial and cytotoxic activity of red propolis: an alert for its safe use

“…According to literature, red propolis is active against yeasts ( Sacharomyces cerevisiae, C. albicans ) and could be an alternative way to solve the multi‐resistance problem to drugs, also being used as an adjuvant in the antifungal treatment with azoic drugs (Lotti et al . ). Superficial mycosis caused by different strains of Candida ( C. glabrata, C. albicans and C. tropicalis) are sensitive to treatments with propolis (Sforcin et al .…”

“…Red propolis has several confirmed biological activities, such as: antimicrobial and antifungal (Siqueira et al 2002;Trusheva et al 2006;Alencar et al 2007;Cabral et al 2009;Lotti et al 2011;Oldoni et al 2011;Righi et al 2011), antioxidant (Alencar et al 2007Cabral et al 2009;Izuta et al 2009a;Oldoni et al 2011;Righi et al 2011), cytotoxic (Alencar et al 2007Awale et al 2008;Li et al 2008;Izuta et al 2009b;Nunes et al 2009;Daleprane et al 2012a,b;Franchi et al 2012;Iio et al 2012;Kamiya et al 2012;Frozza et al 2013), antiparasitic (Ayres et al 2007), hepatoprotective (Rodriguez et al 1997), anti-inflammatory, analgesic and antipsoriasic (Led on et al 1996), wound healing (Albuquerque-J unior et al 2009) and helps to control the lipoprotein metabolism (Iio et al 2010). However, once there are differences in the composition of samples of red propolis (L opez et al 2014), these activities might not be present in all types of red propolis.…”

Investigating the antioxidant and anticytotoxic activities of propolis collected from five regions of Indonesia and their abilities to induce apoptosis

“…Many chemicals cause apoptosis in S. cerevisiae such as glucose, acetic acid and propolis (Sukhanova et al, 2011). The process of apoptosis occurring in S. cerevisiae has been described by Lotti et al (2011). Cytochrome c, but not endonuclease G (Nuc1p), was involved in the propolis-mediated cell death in S. cerevisiae .…”

Susceptibility of Malassezia pachydermatis Clinical Isolates to Allopathic Antifungals and Brazilian Red, Green, and Brown Propolis Extracts

“…All propolis extracts inhibited the growth of isolates presenting a dose-dependent response pattern and antifungal resistance, in concordance with our results. The fungicidal and fungistatic activities of Brazilian green and red propolis extracts are also reportedly observed for other fungi genera, such as Saccharomyces (63) and Trichophyton (64-67).…”