Selective Cytotoxicity of Portuguese Propolis Ethyl Acetate Fraction towards Renal Cancer Cells

Abstract

Renal cell carcinoma is the most lethal cancer of the urological system due to late diagnosis and treatment resistance. Propolis, a beehive product, is a valuable natural source of compounds with bioactivities and may be a beneficial addition to current anticancer treatments. A Portuguese propolis sample, its fractions (n-hexane, ethyl acetate, n-butanol and water) and three subfractions (P1–P3), were tested for their toxicity on A498, 786-O and Caki-2 renal cell carcinoma cell lines and the non-neoplastic HK2 kidney cells. The ethyl acetate fraction showed the strongest toxicity against A498 (IC50 = 0.162 µg mL−1) and 786-O (IC50 = 0.271 µg mL−1) cells. With similar toxicity against 786-O, P1 (IC50 = 3.8 µg mL−1) and P3 (IC50 = 3.1 µg mL−1) exhibited greater effect when combined (IC50 = 2.5 µg mL−1). Results support the potential of propolis and its constituents as promising coadjuvants in renal cell carcinoma treatment.

Phenolic Compounds Contribution to Portuguese Propolis Anti-Melanoma Activity

“…Our research group has previously reported the chemical composition of G18.EE and its fractions [ 43 ]. In general, the compounds found in the subfractions ( Table 2 ) fit well with what has been described for other Gerês propolis samples [ 40 , 42 , 43 ]. Moreover, some of the compounds identified here are present in other European propolis samples [ 64 ].…”

“…Propolis has proven antitumor activity against several types of cancer [ 42 , 47 , 48 , 49 , 50 , 51 , 52 ] and, although scarce, some researchers demonstrated its anti-melanoma activity [ 43 , 53 , 54 ]. Some therapeutic options already exist for melanoma, but their effectiveness is still limited, mainly due to acquired resistance [ 55 ].…”

“…The cytotoxicity of Gerês propolis (G18.EE) and its four fractions: EtOAc, n -hexane, n -BuOH, and water were evaluated in renal cancer cell lines (A498, 786-O and Caki-2) and non-neoplastic renal cells (HK2). The EtOAc fraction was the most effective as it presented considerable cytotoxic activity (IC 50 from 0.16 to 30 µg/mL) and a high selectivity index [ 42 ]. The effect of this Gerês extract and its fractions was previously described in two BRAF -mutated melanoma cell lines.…”

“…Fractionation of G18.EE was performed as previously described [ 42 ]. Succinctly, G18.EE (4 g) was dissolved in absolute ethanol (20 mL) and purified water (200 mL).…”

“…Propolis from Gerês, one of the most studied Portuguese propolis [ 40 , 41 , 42 , 43 , 44 , 45 , 46 ], displays high antioxidant and antimicrobial activities, regardless of the harvesting year [ 40 ]. An ethanol extract of propolis from Gerês collected in 2018 (G18.EE) and its three fractions—ethyl acetate (G18.EE-EtOAc), n -hexane (G18.EE- n -hexane), and n -butanol (G18.EE- n -BuOH)—promoted apoptosis mediated by ROS (reactive oxygen species) in melanoma, thus demonstrating to be cytotoxic to BRAF -mutated melanoma cell lines.…”