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Courtesy of Mike Allen and Steve Gschmeissner

Identification of algal extracts with anti-cancer activity (PHYCONET round 4 PoC)

Principle investigator: Martin Michaelis
University of Kent

Algae are a promising source of bioactive compounds including pharmaceuticals and nutraceuticals.

Examples of algal compounds/ extracts, which have shown biological activity, include those from a range of cyanobacteria, marine microalgae such as Nannochloropsis oculata and the commonly utilised alga Chlorella vulgaris. Less than 1% of the more than 30,000 algal species have been systematically analysed for biological activity. In this proof-of-concept study, we will screen a panel of algal extracts derived from N. oculata (previously described to have anticancer activity) plus Cylindotheca fusiformis, Tetraselmis suecica, Isochrysis galbana, Diacronema lutheri and Tisochrysis lutea for anti-cancer activity. Since there is a lack of information on how culturing conditions affect the levels of bioactivity observed, first standard operation procedures (SOPs) will be developed for the optimised production of algal extracts.

These extracts will then be tested in a unique, well-characterised panel of cancer cell lines that are resistant to clinically relevant anti-cancer drugs. Many tumours respond initially well to therapy (i.e. they shrink or even disappear). However, often cancer cells eventually become resistant to therapy resulting in tumour regrowth, therapy failure, and patient death. This ‘acquired’ drug resistance in cancer represents a major unmet medical need, and novel therapy options are needed.

To study resistance formation in cancer and to identify novel drug candidates, we have established the Resistant Cancer Cell Line (RCCL) collection, the only large collection of cancer cell lines that focuses on acquired drug resistance, currently, consisting of about 1,300 human drug-resistant cancer cell lines. Here, we will test the project algal extracts in a unique panel consisting of 36 breast cancer, lung cancer, ovarian cancer, and neuroblastoma cell lines for which whole exome profiles are available.

This project will provide the proof-of-concept for the discovery, development, and exploitation of novel anti-cancer drug candidates and lead compounds from algae. It will be followed by a multi-disciplinary bioindustrial approach enabled by the complementary expertise of the academic and industrial members of the PHYCONET consortium including the identification of the active ingredients, the modification of lead structures by chemical and/ or synthetic biology approaches, and the development of processing and production platforms. In addition, this project aims to develop and partially de-risk/ streamline the process of discovering novel pharmacologically active agents from algae by developing a practicable and effective biodiscovery pipeline. Whilst the focus here is targeted in the context of anticancer agents, we envisage that we will develop a template that will provide a robust platform for follow on bio-discovery projects to include investigation of extracts/ compounds from algae for further pharmacological/ biological activities.