Isoflavonoids from Brazilian red propolis down‐regulate the expression of cancer‐related target proteins: A pharmacogenomic analysis

Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red propolis, a unique Apis melifera type of propolis botanically originated from Dalbergia ecastophyllum. Although these molecules have relevant biological effects, including anticancer and immunomodulatory activities, their mechanism(s) of action and the affected pathways remain largely unknown. Here, we carried out a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol on the whole‐genome expression in human tumor cells, particularly cancer‐related target proteins. HeLa cells were exposed to the compounds at IC20 and genomic information of treated cells was analyzed using the Illumina transcriptome system and GeneGo MetaCore software. Our results showed that vestitol (IC20 = 214.7 μM) reduced the expression of genes enrolled with the alpha tubulin (fold −3.7), tubulin in microtubules (fold −3.7), and histone h3 (fold = −3.03), and that treatment with neovestitol (IC20 = 102.91 μM) downregulated prostaglandin E synthase gene (fold = −3.12), which are considered ideal targets for anticancer therapy. These data open avenues for the study of vestitol and neovestitol as potential promising candidates for anticancer therapy. Toxicological, non‐clinical, and clinical validation of the findings presented herein is needed.

[1]  S. M. Alencar,et al.  Brazilian red propolis effects on peritoneal macrophage activity: Nitric oxide, cell viability, pro-inflammatory cytokines and gene expression. , 2017, Journal of ethnopharmacology.

[2]  E. Shults,et al.  Phenolic compounds from Glycyrrhiza pallidiflora Maxim. and their cytotoxic activity , 2017, Natural product research.

[3]  Xinrong Ma,et al.  Multiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/triple negative breast cancer , 2016, Oncotarget.

[4]  P. L. Rosalen,et al.  A pharmacological perspective on the use of Brazilian Red Propolis and its isolated compounds against human diseases. , 2016, European journal of medicinal chemistry.

[5]  A. F. Dos Santos,et al.  Brazilian red propolis: phytochemical screening, antioxidant activity and effect against cancer cells , 2015, BMC Complementary and Alternative Medicine.

[6]  I. Baranowska-Bosiacka,et al.  The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. , 2013, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[7]  M. Höglund,et al.  In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues , 2012, Cancer Chemotherapy and Pharmacology.

[8]  P. L. Rosalen,et al.  Isolation and analysis of bioactive isoflavonoids and chalcone from a new type of Brazilian propolis , 2011 .

[9]  E. Perez Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance , 2009, Molecular Cancer Therapeutics.

[10]  C. Costa-Neto,et al.  Chemical composition and biological activity of a new type of Brazilian propolis: red propolis. , 2007, Journal of ethnopharmacology.

[11]  P. L. Rosalen,et al.  Chemical Composition and Botanical Origin of Red Propolis, a New Type of Brazilian Propolis , 2007, Evidence-based complementary and alternative medicine : eCAM.

[12]  A. Giannis,et al.  Epigenetics--an epicenter of gene regulation: histones and histone-modifying enzymes. , 2005, Angewandte Chemie.

[13]  Yi Zhang,et al.  The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. , 2004, Current opinion in genetics & development.

[14]  Yong-Kun Park,et al.  Botanical origin and chemical composition of Brazilian propolis. , 2002, Journal of agricultural and food chemistry.

[15]  C. Allis,et al.  Phosphorylation of Histone H3 Is Required for Proper Chromosome Condensation and Segregation , 1999, Cell.

[16]  A. McPhail,et al.  Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. , 1971, Journal of the American Chemical Society.

[17]  H. Esumi,et al.  Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition. , 2008, Bioorganic & medicinal chemistry.