APPLIED MICROBIAL AND CELL PHYSIOLOGY Partially saturated canthaxanthin purified from Aspergillus carbonarius induces apoptosis in prostrate cancer cell line Nallasamy Kumaresan & Konasur R. Sanjay & Kundumani S. Venkatesh & Ravi-Kumar Kadeppagari & Govindaswamy Vijayalakshmi & Sukumaran Umesh-Kumar Received: 28 November 2007 / Revised: 8 May 2008 / Accepted: 8 May 2008 / Published online: 10 June 2008 # Springer-Verlag 2008 Abstract A mutant Aspergillus carbonarius selected for temperature tolerance after UV treatment, when grown in shake flasks, produced mycelia bearing yellow pigment. Since the mutant was affected in sterol biosynthetic pathway, the pigment was apparently produced to maintain membrane fluidity and rigidity for growth sustenance in low-pH culture broth. Nuclear magnetic resonance analyses characterizing the pigment as a partially saturated cantha- xanthin, containing β-ionone end rings, suggested its application as a retinoid. When tested for this property in retinoic acid receptor expressing prostate cancer cell line, LNCaP, the fungal partially saturated canthaxanthin in- duced apoptosis. Low apoptosis percentage in DU145 prostrate cancer cells that does not express functional retinoic acid receptor-β (RAR-β) suggested binding spec- ificity of the partially saturated canthaxanthin for RAR-β. Keywords Aspergillus carbonarius . Partially saturated canthaxanthin . Apoptosis . LNCaP . DU145 . HeLa . Retinoic acid receptors Introduction Some microorganisms, especially Aspergilli, reduce the pH of culture media to extreme acidity during growth. The internal pH homeostasis, for growth sustenance under such an extreme condition, is maintained either through the cytoplasmic membrane P-adenosine triphosphatases which expel free protons (Serrano 1988; Hesse et al. 2002) or by incorporating sterols, squalene, polyisoprenes (dolichol, ubiquitin), saturated fatty acids, and unusual lipids into the lipid bilayers (Lazrak et al. 1988; Albers et al. 2001) for strongly reducing permeability to water and small molecules. Carotenoids like zeaxanthin, astaxanthin, and canthaxanthin also have the ability to incorporate into membranes and change fluidity and integrity (Wisniewska and Subczynski 1998; Socaciu et al. 2002). While the polar end groups and hydrophobic middle chain of carotenoids have physiological roles in influencing structural and mechanical properties of lipid bilayers to decrease diffusion of free ions (Gabrielska and Gruszecki 1996), the β-ionone rings find application as retinoids for cancer treatment (Bertram 1999; Altucci and Gronemeyer 2001; Garattini et al. 2007). Retinoids, a group of natural and synthetic derivatives of vitamin A (Niles 2004), mediate cell signaling through retinoic acid and retinoid X nuclear receptors to restore normalcy in abnormal animal cells (de Luca 1991; Li et al. 1998; Altucci and Gronemeyer 2001). It involves binding of the retinoid β-ionone end rings to the ligand binding pockets of the receptors (Bertram 1999; Egea et al. 2002). Though efficacy of several synthetic retinoids for cancer therapy have been reported based on studies using cell line models (Huang et al. 1997; Sun et al. 1999; Altucci and Gronemeyer 2001; Bertram and Vine 2005), the occurrence of stereoisomers and toxicity restricted their clinical use (Garattini et al. 2007). Hence, efforts are being made to Appl Microbiol Biotechnol (2008) 80:467–473 DOI 10.1007/s00253-008-1538-7 N. Kumaresan : K. R. Sanjay : G. Vijayalakshmi : S. Umesh-Kumar (*) Food Microbiology Department, Central Food Technological Research Institute, Mysore 570 020, India e-mail: umeshkumar@cftri.res.in Present address: K. S. Venkatesh : R.-K. Kadeppagari Department of Microbiology, Immunology, and Parasitology, Stanley S. Scott Cancer Center, LSU Health Sciences Center, New Orleans, LA 70112-1393, USA