Cytotoxicity and Pro-Apoptotic, Antioxidant and Anti-Inflammatory Activities of Geopropolis Produced by the Stingless Bee Melipona fasciculata Smith.

Josianne Rocha Barboza,Isabella Dos Santos Guimarães,Alberto Jorge Oliveira Lopes,Francisco Assis Nascimento Pereira,Andreia Cristina De Melo,Maria Nilce De Sousa Ribeiro,Cláudia Quintino Da Rocha,Cleydlenne Costa Vasconcelos,Maria Do Socorro De Sousa Cartágenes,Renan Amphilophio Fernandes

doi:10.3390/biology9090292

Abstract

Geopropolis is produced by some stingless bee species, such as Melipona fasciculata Smith, a native species from Brazil. This study aims to investigate the antioxidant and anti-inflammatory activities and cytotoxicity effects of geopropolis hydroethanolic extracts against lung (H460 and A549) and ovarian (A2780 and ES2) cancer cell lines and non-tumor (HUVEC) cell lines using chemical identification by LC/MS/MS analysis and in silico assays to determine which compounds are associated with bioactivity. The antioxidant activity of extracts and inhibitory activity against COX enzymes were assessed by in vitro assays; cytotoxicity effect was evaluated by the MTT assay; cell cycle was assessed by flow cytometry and apoptosis by Western blotting. The geopropolis extracts showed great radical scavenging potential, preferential inhibition of COX-2, decreased cancer cell viability, non-cytotoxic effects against the non-tumoral cell line, besides modulating the cell cycle and inducing cancer cell apoptosis through the activation of caspase-3 and PARP protein cleavage. The in silico study suggests that corilagin, typhaneoside, taraxerone and marsformosanone, identified by LC/MS/MS, can be associated with anti-inflammatory activity and cytotoxic effects. Thus, the current study suggests the potential of geopropolis concerning the research field of new pharmacological alternatives regarding cancer therapy.

Highlights

Cancer arises from the gradual accumulation of genetic alterations that increase cell proliferation [1].It is the second main cause of death and has been recognized as one of the major public health problems worldwide
The results show that EHGV had the highest antioxidant activity with DPPH inhibitory concentration at 50% (IC50) (76.16 ± 1.05 μg/mL)
Our findings indicate that EHGV demonstrated higher cytotoxic effects at 48 and 72 h compared to EHGP in all cancer cell lines (Figure 3)

Summary

Introduction

Cancer arises from the gradual accumulation of genetic alterations that increase cell proliferation [1]. It is the second main cause of death and has been recognized as one of the major public health problems worldwide. In 2018 alone, over 18 million new cancer cases were reported and over 9.5 million deaths by cancer were recorded worldwide, according to GLOBOCAN [2]. The development of new alternative drugs exhibiting low toxicity, high efficiency and the ability to prevent cell proliferation and/or promote apoptosis has become the major focus of cancer therapy in recent years [4,5]. In addition to apoptosis-inducing drugs, anti-inflammatory agents selective for cyclooxygenase

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