Abstract
From all types of cancer, cervical cancer manages to be in top four most frequent types, with a 6.5% rate of occurrence. The infectious vector that induces the disease, the high-risk Human papillomavirus (HPV), which is a sexually transmitted virus, is capable of transforming the host cell by modulating some of the principal signaling pathways responsible for cell cycle arrest, proliferation, and survival. Fortunately, like other cancer types, cervical cancer can be treated by chirurgical interventions or chemoradiotherapy, but these methods are not exactly the lucky clover of modern medicine because of the adverse effects they have. That is the reason why in the last years the emphasis has been on alternative medicine, more specifically on phytochemicals, as a substantial number of studies showed that diet contributes to cancer prevention and treatment. All these studies are trying to find new chemopreventive agents with less toxicity but high effectiveness both in vitro and in vivo. The aim of this review is to evaluate the literature in order to underline the advantages and disadvantages of polyphenols, a class of dietary compounds, as chemopreventive and chemotherapeutic agents. This review also aims to present polyphenols from different perspectives, starting with mechanisms of action and ending with their toxicity. The bigger picture illustrates that polyphenols have great potential in cervical cancer prevention, with strong effects on gene modulation.
Highlights
Cancer is one of the leading causes of death, with cervical cancer being the fourth most common cancer type among women worldwide [1]
The Human papillomavirus (HPV) oncoprotein E5 increases the phosphorylation level of epidermal growth factor receptor (EGFR), which lead to hyperproliferation (Figure 4c) [23]; PI3K/Akt/mTOR: This signaling cascade targets some of the most important and complex intracellular processes, which are triggered by a series of internal and external stimuli such as cell proliferation, apoptosis, energy metabolism, growth, and migration
The E6 oncoprotein can upregulate the expression of extracellular signal-regulated kinase (ERK) and both the E6 and E7 oncoproteins can regulate hypoxia-inducible factor 1α (HIF-1α), interleukine-8 (IL-8), and the vascular endothelial growth factor (VEGF), which can lead to high rates of proliferation, differentiation, and angiogenesis (Figure 4c) [23,27–29]; AP-1: The activating protein-1 (AP-1) is an early transcription factor that plays an essential role in the transcription regulation of the HPV genome
Summary
Cancer is one of the leading causes of death, with cervical cancer being the fourth most common cancer type among women worldwide [1]. Numerous studies have shown that cervical cancer cannot be triggered only by one factor [3]. Radiotherapy and chemotherapy are used to treat this type of cancer. All these therapies have shown signs of major side effects such as bleeding, damage to the organs around the surgery, and the risk of clots. Cisplatin or other drugs that are usually prescribed for cervical cancer can lead to major side effects or even drug resistance [5]. Studies have shown strong evidence that natural compounds such as polyphenols or other phytochemicals can potentially regulate gene expression by targeting different components of the genetic and epigenetic machinery [4]. Polyphenols are promising anti-cervical cancer agents, their poor solubility and low oral bioavailability obstruct their potential clinical application [3]
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