Selenium-enriched Arthrospira platensis potentiates docetaxel, oxaliplatin, and topotecan anticancer activity in epithelial tumors
- 234 Downloads
Docetaxel (DOC), oxaliplatin (OXA), and topotecan (TOPO) are effective chemotherapy agents in human cancers, but their clinical use is limited by severe side effects. Arthrospira platensis, a cyanobacterium that is widely used as a nutritional supplement, can accumulate in a dose- and time-dependent manner high amounts of selenium (Se), a trace element with potential anticancer effects. In this study, we (1) tested the in vitro effects of A. platensis enriched with Se alone or combined with DOC, OXA, or TOPO (IC50 concentrations) on cell proliferation, in situ apoptosis, and reactive oxygen species (ROS) production in human epithelial colorectal adenocarcinoma (Caco-2) and prostate cancer (DU145) cell lines and (2) assessed the in vivo effect on tumor growth in mice xenografted with renal carcinoma cells (RCC 786-0). Neither Se nor Se-enriched A. platensis affected the viability significantly. Incubation of Caco-2 or DU145 cells with Se + DOC, Se + OXA, or Se + TOPO-enriched A. platensis increased significantly the cytotoxicity of each drug by 85–99 % (compared with cells treated with anticancer drug alone) through promotion of caspase-3-mediated apoptosis and reduction of ROS production. In vivo, treatment with Se + TOPO-enriched A. platensis for 4 weeks significantly reduced tumor growth compared with placebo or Se-enriched A. platensis alone (p < 0.05). The Se + antimitotic drug-enriched A. platensis formulation using Se-enriched A. platensis as a vector for anticancer drug delivery could represent a new strategy for the development of effective and less toxic treatments against cancer.
KeywordsArthrospira platensis Spirulina Selenium Anticancer agent Epithelial tumor
The authors wish to thank Dr. Y. Rustum from the Cancer Biology Department, Roswell Park Memorial Institute, Elm and Carlton Street, Buffalo, for his help with the in vivo experiments and Dr. E. Andermarcher for correcting the English.
Compliance with ethical standards
The Institutional Animal Experimentation Ethics Committee approved this study.
C.R. and H.O. contributed equally to the research concept and design. H.O. reviewed the manuscript and C.R. researched the data, wrote and edited the manuscript, and is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the data integrity and the accuracy of the data analysis.
The authors are co-inventors of the French patent # FR1257009.
- Chintala S, Najrana T, Toth K, Cao S, Durrani FA, Pili R, Rustum YM (2012) Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition. BMC Cancer 12:293. doi: 10.1186/1471-2407-12-293 CrossRefPubMedPubMedCentralGoogle Scholar
- Durrani FA, Chintala S, Toth K, Cao S, Rustum YM (2015) Mechanism-based drug combination targeting HIF-2α and VEGF in renal cancer xenografts. Trends Cell Mol Biol 10:77–89Google Scholar
- Koníčková R, Vaňková K, Vaníková J, Váňová K, Muchová L, Subhanová I, Zadinová M, Zelenka J, Dvořák A, Kolář M, Strnad H, Rimpelová S, Ruml T, J Wong R, Vítek L (2014) Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds. Ann Hepatol 13:273–283PubMedGoogle Scholar
- Lee P, Zhang R, Li V, Liu X, Sun RW, Che CM, Wong KK (2012) Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulation. Int J Nanomed 7:731–737Google Scholar
- Mosulishvili LM, Kirkesali EI, Belokobylsky AI, Khizanishvili AI, Frontasyeva MV, Pavlov SS, Gundorina SF (2002) Experimental substantiation of the possibility of developing selenium- and iodine-containing pharmaceuticals based on blue-green algae Spirulina platensis. J Pharm Biomed Anal 30:87–97CrossRefPubMedGoogle Scholar
- Oreal H, Riva-Laveille C (2012) Integration de molécules actives dans des microalgues séléniées, French Patent Application FR1257009Google Scholar
- Riss J, Décordé K, Sutra T, Delage M, Baccou JC, Jouy N, Brune JP, Oréal H, Cristol JP, Rouanet JM (2007) Phycobiliprotein C-phycocyanin from Spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric Food Chem 55:7962–7967CrossRefPubMedGoogle Scholar
- Soccol CR, Porto de Souza Vandenberghe L, Rigon Spier M, Pedroni Medeiros AB, Tiemi Yamaguishi C, De Dea Lindner J, Pandey A, Thomaz-Soccol V (2010) The potential of probiotics: a review. Food Tech Biotech 48:413–434Google Scholar
- Zarrouk C. (1966) Contribution a l’etude d’une cyanophycee. Influence de divers facteurs physiques et chimiques sur la croissance et la photosynthese de Spirulina maxima (Setch. et Gardner) Geitler. Ph.D. Thesis, University of Paris, France.Google Scholar
- Zhang H, Chen T, Jiang J, Wong YS, Yang F, Zheng W (2011) Selenium-containing allophycocyanin purified from selenium-enriched Spirulina platensis attenuates AAPH-induced oxidative stress in human erythrocytes through inhibition of ROS generation. J Agric Food Chem 59:8683–8690CrossRefPubMedGoogle Scholar