American Journal of Ethnomedicine

Cuban propolis and nemorosone in combination with chemotherapeutic agents induce a synergistic cytotoxic effect in drug-resistant human colon carcinoma cells

7^th Edition of International Conference on Pharmacognosy and Medicinal Plants
March 11-12, 2019 London, UK

Y Frion-Herrera, D Gabbia and M Carrara

University of Padova, Italy

Posters & Accepted Abstracts: Am J Ethnomed

DOI: 10.21767/2348-9502-C1-009

Abstract

Propolis is a resinous product collected by honeybees from the buds and exudates of various plant sources. This natural product has been used empirically as a traditional remedy in folk medicine for centuries. Several studies have confirmed that propolis mono-therapy can inhibit the growth of different carcinoma cells due to its chemical composition. At present, there are few studies about the possible use of this natural product in the treatment of chemo-resistant tumors. Combination experiments were carried out in order to study the ability of Cuban propolis extracts (CP) and nemorosone, its main phytocomponent, to increase the antiproliferative efficacy of traditional cytotoxic chemotherapic drugs doxorubicin (Dox) and oxaliplatin (Oxa) in human colon carcinoma cells (LoVo), doxorubicin resistant cells (LoVo Dox) and oxaliplatin resistant cells (LoVo Oxa). The effects of combination therapy were investigated in vitro, evaluating cell viability at 24, 48 and 72 hrs by MTT assay. Synergism/additivity/antagonism effect was assessed by isobologram/combination index analysis. Molecular mechanism of combination treatment was examined assessing LDH release, Annexin/PI assay, ROS production, mitochondrial membrane potential (ΔΨm) disturbance and ATP intracellular levels. Our results revealed that combination treatment resulted in a significantly synergistic antiproliferative and cytotoxic effect at 72 hrs with respect to monotherapy, in particular in drugresistant cell lines. Furthermore, combined treatment induced apoptosis cell death with a marked disruption of ΔΨm, decrease in ATP production and induction of ROS. These findings indicate that combination of CP or nemorosone with classical chemotherapic drugs may represent an intriguing treatment option for drugresistant human colon carcinoma.