Natural products as a source of anti-cancer agents

Natural products are important resources for drug discovery. At least a quarter of new chemical entities (NCEs) introduced within last 25 years are either natural products or derived from natural products, and more than a half of them originated from plants.

The plants from Annonaceae family, especially, Annona muricata (also known as soursop, graviola and guanabana), have been widely used as a natural medicinal remedy, and a broad range of therapeutic effects has been reported, including anti-bacterial, anti-inflammatory, and anti-tumour activities. The latter was documented in a number of articles, dating back as far as the1990’s, in which acetogenins, purified from the soursop extracts, had the potential to kill breast, prostate, pancreas, skin and liver cancer cells shown in vitro and, to some extent, in vivo. However, these data do not look very convincing in modern times. This is evident from Cancer Research UK who clearly stated on their webpage that they do not support the use of graviola (soursop) to treat cancer as there have not been any large scale studies in humans on the use of graviola for cancer therapy and no substantial evidence of its anti-cancer activity exists. At the same time, from another angle, this warrants an official study of graviola as a potential drug for cancer chemotherapy which we have recently initiated.

Brunel Biosciences is leading the multidisciplinary international collaboration that includes the Brunel Institute for Bioengineering, Middlesex University London and University of the West Indies, Trinidad & Tobago, and aims to address the anti-cancer properties of individual components extracted from fruit soursop at the highest methodological level. Our Trinidad & Tobago collaborators are able to prepare large quantities of different soursop extracts and carry out initial flash chromatography fractionations. The chemicals will be purified using HPLC and CCC (Counter-Current Chromatography), a unique separation technique (and equipment) developed at the Brunel Institute for Bioengineering. The purified components will be tested in a number of cell viability and toxicity assays using a broad collection of cell lines present within the Biosciences department. The emphasis of this project will be on identification of cellular targets of compounds from soursop – which pathway is affected and expression of which genes is altered? – these are the main questions for which a PhD student is supposed to find the answers.

The bench work will include a wide variety of modern cell biology techniques: real-time RT-PCR, microarrays, siRNA knockdown, confocal microscopy and live cell imaging.

Our interest in natural products is not limited to fruit soursop. We will consider applications which propose purifications and biological characterisation of compounds from the other natural products if the source of starting material is provided by an applicant.

Brunel University is an equal opportunities employer. We welcome applications from Home/EU and Overseas self-funded students who meet the entry requirements and able to cover all the costs, including tuition fees, bench fees and living expenses. The required information is available on the Brunel Research webpage (http://www.brunel.ac.uk/research/research-degrees-at-brunel) following the appropriate links. Informal enquiries sent directly to Dr. Evgeny Makarov ([Email Address Removed]) are advisable prior to a formal application to the Brunel PhD Programme.