The Involvement of Natural Polyphenols in the Chemoprevention of Cervical Cancer

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.

Keywords: HPV; apoptosis; cervical cancer; phytochemicals; polyphenols; toxicity.

Figure 1

Mortality and incidence rate of cervical cancer worldwide (per 100,000 individuals) (adapted after Khazaei et al., 2019 [2]).

Figure 2

Estimated number of new cases of cancer in 2020 among women of all ages worldwide (adapted after “GLOBOCAN 2020: New Global Cancer Data | UICC.” [1]).

Figure 3

HPV genome (adapted after Bowden and Kyrgiou, 2020 [18]).

Figure 4

The impact of HPV viral proteins on the main signaling pathways responsible for cell survival, proliferation, and differentiation: (a) the effect of the E6 oncoprotein on the p53 tran-scription factor; (b) the effect of the E7 oncoprotein on the pRb tumor-suppression protein; and (c) the effects of the E5, E6, and E7 oncoproteins on EGFR phosphorylation, the PI3K/Akt/mTOR pathway, JNK, ERK, and the AP-1 complex.

Figure 4

The impact of HPV viral proteins on the main signaling pathways responsible for cell survival, proliferation, and differentiation: (a) the effect of the E6 oncoprotein on the p53 tran-scription factor; (b) the effect of the E7 oncoprotein on the pRb tumor-suppression protein; and (c) the effects of the E5, E6, and E7 oncoproteins on EGFR phosphorylation, the PI3K/Akt/mTOR pathway, JNK, ERK, and the AP-1 complex.

Figure 5

Classification of polyphenols.

Figure 6

Potential mechanisms of action of polyphenols on epigenetic pathways.