Abstract

There is a strong need to develop new drugs against many severe diseases. Therapy resistance is a major problem in, for instance, infectious diseases and cancer. Drug discovery has again turned to nature to search for molecules that can become drug leads. Although many bacterial phyla are extensively studied, some, like the Planctomycetes, remain largely unexplored as potential sources of new leads. Planctomycetes form a diverse group of bacteria with peculiar characteristics such as division by polar budding and absence of the FtsZ gene. Furthermore, they exhibit large genomes up to 12.5 Mb, and possess a high number of secondary metabolites as assessed by in silico genomic analysis. These characteristics have also revealed the presence of potential anticancer activity. Based on these promising characteristics, we wanted to investigate Planctomycetes as a source for natural products with anticancer properties. Organic and aqueous extracts were obtained from cultivated Planctomycetes strains originated from a variety of habitats such as marine systems (free living or attached to marine algae), deep marine iron hydroxide deposits, brackish water and glacier ice system. The extracts were screened for ability to inhibit cell growth, or induce cell death on two cancer cell lines, the human prostatic cancer cell line PC3, and human acute myeloid leukaemia (AML) cell line MOLM-13, as well as normal rat kidney epithelial cell line (NRK). Out of 39 strains, five exhibited cytotoxicity towards NRK cells, whereas 32 of the strains were toxic to the AML cell line, and four were toxic to the PC3 cell line. Two strains showed high toxicity and selectivity towards both the cancer cell lines over the NRK-cells, and are potential producers of anti-cancer compounds. We found no correlation between bioactivity and strains habitat and geographic location but regarding phylogeny some Rhodopirellula spp. showed higher toxicity toward MOLM-13 cells. These results from the first anticancer screening with Planctomycetes showed that these peculiar microorganisms should be further explored for anti-cancer compounds and that more effort must be put in providing culture collections for drug development purposes.

Highlights

  • Biotechnological search for new natural products is of utmost importance for the well-being and sustainability of humanity in the fight against many deadly diseases such as cancer and bacterial infections due to development of drug resistance (O’Neill, 2016)

  • A total of 39 Planctomycetes were screened for cytotoxic bioactivity toward human acute myeloid leukaemia (AML) cell line (MOLM-13) and human prostatic cancer cell line (PC3)

  • The normal rat kidney epithelial cell line (NRK) was used to be able to distinguish between general cytotoxic activity, and anti-cancer activity

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Summary

Introduction

Biotechnological search for new natural products is of utmost importance for the well-being and sustainability of humanity in the fight against many deadly diseases such as cancer and bacterial infections due to development of drug resistance (O’Neill, 2016). In Europe, cancer represents the second most important cause of death and morbidity with more than 3.7 million new cases and 1.9 million deaths each year (World Health Organization, 2012). In the United States, values of 1.7 million new cancer cases diagnosed and 0.6 million cancer deaths were estimated for 2017 (Siegel et al, 2017). As the prophylactic treatment to prevent cardiovascular diseases improves, it is expected that cancer will become the leading cause of death within few years (Heron and Anderson, 2016). This increase in cancer incidents represents new challenges. There will be a need for novel therapeutics with less harmful side-effects like cardiac failure or bone marrow depletion, often associated with therapy-induced mortality in elderly patients

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