Bacterioruberin: Biosynthesis, Antioxidant Activity, and Therapeutic Applications in Cancer and Immune Pathologies.

Halophilic archaea, also termed haloarchaea, are a group of moderate and extreme halophilic microorganisms that constitute the major microbial populations in hypersaline environments. In these ecosystems, mainly aquatic, haloarchaea are constantly exposed to ionic and oxidative stress due to saturated salt concentrations and high incidences of UV radiation (mainly in summer). To survive under these harsh conditions, haloarchaea have developed molecular adaptations including hyperpigmentation. Regarding pigmentation, haloarchaeal species mainly synthesise the rare C50 carotenoid called bacterioruberin (BR) and its derivatives, monoanhydrobacterioruberin and bisanhydrobacterioruberin. Due to their colours and extraordinary antioxidant properties, BR and its derivatives have been the aim of research in several research groups all over the world during the last decade. This review aims to summarise the most relevant characteristics of BR and its derivatives as well as describe their reported antitumoral, immunomodulatory, and antioxidant biological activities. Based on their biological activities, these carotenoids can be considered promising natural biomolecules that could be used as tools to design new strategies and/or pharmaceutical formulas to fight against cancer, promote immunomodulation, or preserve skin health, among other potential uses.

Haloarchaeal carotenoids exert an in vitro antiproliferative effect on human breast cancer cell lines.

Oxidative stress has been linked to the onset and progression of different neoplasia. Antioxidants might help prevent it by modulating biochemical processes involved in cell proliferation. Here, the aim was to evaluate the in vitro cytotoxic effect of Haloferax mediterranei bacterioruberin-rich carotenoid extracts (BRCE) (0-100 µg/ml) in six BC cell lines, representative of the intrinsic phenotypes and a healthy mammary epithelium cell line. Cell index values were obtained using xCELLigence RTCA System. Furthermore, cell diameter, viability, and concentration were measured at 12 h, 24 h, and 30 h. We found that BC cells were selectively affected by BRCE (SI > 1, p < 0.005). After 30 h, the population of BC cells exposed to 100 µg/ml was 11.7-64.6% of the control (p = 0.0001-0.0009). Triple-negative cells were significantly affected [MDA-MB-231 (IC50 51.8 µg/ml, p < 0.0001) and MDA-MB-468 (IC50 63.9 µg/ml, p < 0.0001)]. Cell size was also reduced after 30 h treatment in 3.8 (± 0.1) µm and 3.3 (± 0.02) µm for SK-BR-3 (p < 0.0001) and MDA-MB-468 (p < 0.0001), respectively. In conclusion, Hfx. mediterranei BRCE exerts a cytotoxic effect on BC cell lines representative of all studied intrinsic subtypes. Furthermore, results obtained for MDA-MB-231 and MDA-MB-468 are very promising, considering the aggressive behaviour of the triple-negative BC subtype.

Carbon Source Influences Antioxidant, Antiglycemic, and Antilipidemic Activities of Haloferax mediterranei Carotenoid Extracts.

Haloarchaeal carotenoids have attracted attention lately due to their potential antioxidant activity. This work studies the effect of different concentrations of carbon sources on cell growth and carotenoid production. Carotenoid extract composition was characterized by HPLC-MS. Antioxidant activity of carotenoid extracts obtained from cell cultures grown under different nutritional conditions was determined by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Ability Power (FRAP) and ß-carotene bleaching assays. The ability of these carotenoid extracts to inhibit α-glucosidase, α-amylase, and lipase enzymes was also assessed to determine if they could be used to reduce blood glucose and lipid absorption. The maximum production of carotenoids (92.2 µg/mL) was observed combining 12.5% inorganic salts and 2.5% of glucose/starch. Antioxidant, hypoglycemic, and antilipidemic studies showed that higher carbon availability in the culture media leads to changes in the extract composition, resulting in more active haloarchaeal carotenoid extracts. Carotenoid extracts obtained from high-carbon-availability cell cultures presented higher proportions of all-trans-bacterioruberin, 5-cis-bacterioruberin, and a double isomeric bacterioruberin, whereas the presence 9-cis-bacterioruberin and 13-cis-bacterioruberin decreased. The production of haloarchaeal carotenoids can be successfully optimized by changing nutritional conditions. Furthermore, carotenoid composition can be altered by modifying carbon source concentration. These natural compounds are very promising in food and nutraceutical industries.

Halophilic Carotenoids and Breast Cancer: From Salt Marshes to Biomedicine.

Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor-RE-/progesterone receptor-PR) and growth factor receptor (human epidermal growth factor receptor-HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea.