How Can NMR Help To Identify Novel Cervical Cancer Treatments?

Cervical cancer is the fourth most commonly occurring cancer in women and the eighth most commonly occurring cancer overall. Globally, there were over 500,000 new cases in 20181.

Virtually all cervical cancers are associated with Human papillomaviruses (HPVs)2. However, the presence of HPV does not mean a woman will develop cervical cancer. HPV infection will increase the susceptibility to developing cervical cancer, but other environmental factors are required for the cancer to develop.

Treatment to prevent cervical cancer spreading is required as soon as possible to avoid a more severe disease course. This is usually achieved by ablation of the abnormal cells by surgical excision, chemotherapy, or cryotherapy. Although effective, such procedures are not ideal due to the excessive tissue damage that can occur. Consequently, there is ongoing research to develop an efficient but safer alternative.  

HPV

HPV viruses can cause life-long debilitating diseases, not least by increasing the risk of developing cervical cancer, and these may significantly reduce a patient’s quality of life. High-risk HPV infections interfere with the molecular pathways that are responsible for regulating epithelial differentiation as well as cell proliferation3. The virus releases oncoproteins that effect cellular changes in HPV infected cells that prevent the infection from being eliminated and interfere with transcription regulation mechanisms.

The presence of even minimal amounts of HPV DNA can increase the risk of developing cervical cancer. Inactivation of the HPV would therefore effectively reduce the risk of developing cervical cancer. However, no such treatment is currently available.

Therapeutic activity of Ficus carica

The common fig (Ficus carica) is a small tree native to southwest Asia that is widely cultivated for commercial sale of the fruit. Although juicy and sweet when ripe, the figs are gummy with latex when unripe. This fruit latex has been shown to heal skin lesions, such as warts, caused by HPV4. It thus has potential as a possible cure for HPV infections without the risk of tissue injury. However, the mechanisms of action of the biologically active components of the Ficus carica latex remain poorly understood.

fig tree

© Anuwat Khamngoen/Shutterstock.com

A recent in vitro study investigated the biological activities of fig latex against a cervical cancer cell line (CaSki) and immortal HeLa cells infected with HPV5. The chemical composition of fig latex was also analyzed to gain insight into the possible mechanisms of action by which it deactivates HPV.  This was performed using a series of nuclear magnetic resonance (NMR) and mass spectroscopy (MS) analyses using a Bruker Avance III 600 MHz NMR spectrometer and a Bruker time-of-flight MicrOTOF Focus mass spectrometer, respectively.

The fig latex was shown to have anti-cancer activity, inhibiting the properties of treated cells that are associated with HPV-positive cervical cancer transformed cells5. It inhibited the growth of cervical cancer cells, induced of apoptosis, prevented colony formation, and cell proliferation and transformation and downregulated the expression of HPV oncoproteins. Further investigations revealed that the fig latex influences cell growth in cervical cancer cells by targeting the Ki67 protein.

In addition to its potent anti-cancer effects, the fig latex had a profound influence on the deregulation of HPV oncoproteins and an HPV diagnostic marker protein and initiated the reactivation of tumor suppressor proteins. No toxic effects were observed on the control of human immortalized keratinocyte (HaCaT) cells.

 

NMR and MS analyses of the crude fig latex, aqueous supernatant and polymeric gum of fig latex identified for the first time a chemical component that is likely to provide the anti-HPV activity. This component is likely to be lipophilic and possibly a chlorogenic/ferrulic/caffeic acid plant sterol derivative.

These findings suggest that Ficus carica latex has the potential to be used in the development of therapeutic modalities for the possible treatment, cure and prevention of HPV-related cervical cancer.  Isolation and identification of the purported active component of the fig latex in future studies will inform drug screening programs to identify an effective and safe potential treatment for HPV infection.

References

  1. World Health Organization Cancer 2018. Available at http://www.who.int/news-room/fact-sheets/detail/cancer
  2. Salman N, et al. Association of High Risk Human Papillomavirus and Breast cancer: A UK based Study. Sci. Rep. 2017;7:43591.
  3. Ramakrishnan S, et al. Overview of high-risk HPV’s 16 and 18 infected cervical cancer: Pathogenesis to prevention. Biomed. Pharmacother. 2015;70:103–110.
  4. Bohlooli S, et al. Comparative study of fig tree efficacy in the treatment of common warts (Verruca vulgaris) vs. cryotherapy. Int. J. Dermatol. 2007;46:524–526.
  5. Ghanbari A, et al. Biological activities of Ficus carica latex for potential therapeutics in Human Papillomavirus (HPV) related cervical cancers. Scientific Reports 2019; 9:Article number 1013.

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Last updated: Jul 30, 2019 at 6:53 AM

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