Emodin, Physcion, and Crude Extract of Rhamnus sphaerosperma var. pubescens Induce Mixed Cell Death, Increase in Oxidative Stress, DNA Damage, and Inhibition of AKT in Cervical and Oral Squamous Carcinoma Cell Lines.

Thais Fernanda Moreira,Obdulio Gomes Miguel,Christiane Pienna Soares,Barbara Colatto Fernandes,Amanda Martins Baviera,Renata Pires Assis,Daniella Maria Soares De Oliveira,Felipe De Oliveira Souza,Fernanda Maria Marins Ocampos,Carlos Alberto Arcaro,Juliana Maria Sorbo,Andersson Barison,Iguatemy Lourenço Brunetti

doi:10.1155/2018/2390234

Thais Fernanda Moreira, Obdulio Gomes Miguel + Show 11 more

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https://doi.org/10.1155/2018/2390234

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Abstract

There have been few studies on the pharmacological properties of Rhamnus sphaerosperma var. pubescens, a native Brazilian species popularly known as “fruto-de-pombo.” The aim of this study was to investigate the scavenging capacity of emodin, physcion, and the ethanolic crude extract of Rhamnus sphaerosperma var. pubescens against reactive oxygen and nitrogen species, as well as their role and plausible mechanisms in prompting cell death and changes in AKT phosphorylation after cervical (SiHa and C33A) and oral (HSC-3) squamous cell carcinoma treatments. Emodin was shown to be the best scavenger of NO• and O2•−, while all samples were equally effective in HOCl/OCl− capture. Emodin, physcion, and the ethanolic extract all exhibited cytotoxic effects on SiHa, C33A, HSC-3, and HaCaT (immortalized human keratinocytes, nontumorigenic cell line), involving mixed cell death (apoptosis and necrosis) independent of the caspase activation pathway. Emodin, physcion, and the ethanolic extract increased intracellular oxidative stress and DNA damage. Emodin decreased the activation of AKT in all tumor cells, physcion in HSC-3 and HaCaT cells, and the ethanolic extract in C33A and HaCaT cells, respectively. The induction of cancer cell death by emodin, physcion, and the ethanolic crude extract of Rhamnus sphaerosperma var. pubescens was related to an increase in intracellular oxidative stress and DNA damage and a decrease in AKT activation. These molecules are therefore emerging as interesting candidates for further study as novel options to treat cervical and oral carcinomas.

Highlights

Cancer is a major global health concern
In addition to cervical cancer, human papillomavirus (HPV) is associated with the induction of other types of cancer, including squamous cell carcinoma of the esophagus and oral cavity [1,2,3,4]
The present study identified different responses of the anthraquinones emodin and physcion and crude extracts from Rhamnus sphaerosperma var. pubescens related to the ability to capture reactive oxygen and nitrogen species

Summary

Introduction

Cancer is a major global health concern. High morbidity and mortality rates indicate an increase in the global incidence of cancer, mainly owing to aging populations. Cervical cancer is the fourth most common cancer diagnosed in women worldwide; it is associated with human papillomavirus (HPV) infection. Despite vaccination efforts against HPV infections, since vaccines may provide cross-protection against some HPV strains known to cause cervical cancer, a Oxidative Medicine and Cellular Longevity considerable number of female deaths is still attributed to cervical cancer [1]. In addition to cervical cancer, HPV is associated with the induction of other types of cancer, including squamous cell carcinoma of the esophagus and oral cavity (oropharynx, tonsils, and tongue) [1,2,3,4]

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