Human papillomavirus, cervical carcinogenesis and chemoprevention with Indole derivates – a review of pathomechanisms

Abstract

Cervical cancer is the second most common female cancer worldwide with high risk Human Papillomavirus (HPV) infection playing an essential aetiological role. Oestrogen interacts with HPV at a cellular level causing cell growth and inhibition of apoptosis. Indole derivatives, formed during digestion of cruciferous vegetables, have been shown to have chemopreventative properties inhibiting HPV transcription and influencing oestrogen metabolism. This review describes the interactions between HPV, oestrogen and indole derivatives. Further clinical research is required to evaluate the chemopreventative properties of these agents.

Protective action of indole‐3‐acetic acid on induced hepatocarcinoma in mice

“…34 Several antitumor and chemopreventive properties for indole compounds have been studied in vivo and in vitro. 4 Accordingly, this work showed for the first time that IAA has a hepatocarcinogenesis protection validated by means of a DEN-protective effect on CAT and GR activity, antioxidant gene expression, and DNA fragmentation data.…”

“…[1][2][3] Indoles were found in Brassicas (cruciferous vegetables such as cauliflower, brussel sprouts, broccoli, and others) and have been shown to have chemopreventive properties. 4,5 Indole-3-acetic acid (IAA) is an indole compound that can be synthesized in plants, microorganisms and animals including mammals. Animals can obtain IAA from intestinal absorption of a diet rich in vegetables or from synthesis from tryptophan in various tissues.…”

“…15 The prevention of several diseases by many natural substances has been associated with the antioxidant action of these compounds upon depletion of reactive oxygen species (ROS). 4,5 Accumulation of intracellular ROS during extended periods of oxidative stress accompanies the development of many chronic diseases, including liver disorder and cancer. 16 However, the cells have efficient molecular strategies to strictly control intracellular ROS levels and to maintain the balance between oxidant and antioxidant molecules.…”

“…19 There is extensive evidence that ROS participate in DENinduced hepatocarcinogenesis. 20 Recent work shows that indole compounds have been studied in vivo and in vitro as antitumor and chemopreventive agents, 4 but no studies have been reported on the protective effects of IAA on induced carcinogenesis.…”

Identification of Androgen Receptor and Beta-Catenin Target Genes in Prostate and Prostate Cancer

“…Also, a drug that can reduce estrogen signaling, Indole-3-carbinol (I3C), prevents cervical cancer in HPV16-infected mice and was highly effective in inducing precancerous lesion regression in women (24)(25)(26). These effects may be due to the fact that I3C can also degrade β-catenin in prostate cancer cells (27). Given these facts, I hypothesized that HPV infection leads to increased activity of β-catenin, which contributes to the development of cervical cancer by up-regulating ERα targets.…”