Standardized Extract of the Persian Gulf Sponge, Axinella Sinoxea Selectively Induces Apoptosis through Mitochondria in Human Chronic Lymphocytic Leukemia Cells


  • Ahmad Salimi Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Mehrnoush Pir Saharkhiz Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Abbasali Motallebi Research and Education and Extension Organization (AREEO) and Iranian Fisheries Research Organization, Ministry of Jihad-e-Agriculture, Tehran, Iran
  • Enayatollah Seydi Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Ali Reza Mohseni Department of Laboratory Sciences, Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Iran
  • Melika Nazemi Iranian Fisheries Research Institute, Persian Gulf and Oman Sea Ecological Research, Agricultural Research, Education and Extension Organization (AREEO), Bandar Abbas, Iran
  • Jalal Pourahmad Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran



Sponge, Axinella sinoxea, Mitochondria, Chronic Lymphocytic Leukemia.


 Sponges are important components of the Persian Gulf animal communities. The marine sponges of the genus Axinella sinoxea is are a genus of sponges in the family Axinellidae. Species of Axinella sinoxea occur in the India, Pacific Oceans and also Persian Gulf. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5+ B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes mitochondria (both cancerous and non-cancerous) were isolated using differential centrifugation from peripheral blood samples and succinate dehydrogenase activity, mitochondrial reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP), mitochondrial swelling and finally release of cytochrome C were examined following the addition of methanolic extract of Axinella sinoxea. Our results showed that only in mitochondria isolated from cancerous BUT NOT normal lymphocytes a significant (P < 0.05) increase in mitochondrial ROS formation, MMP collapse, mitochondrial swelling and cytochrome c release. These results showed that Axinella sinoxea extract has a selective toxicity on chronic lymphocytic leukemia lymphocytes and their mitochondria and hence may be considered as a promising anti CLL candidate for further studies needed as a supplement for cancer patients in the future.


Faulkner DJ. Marine pharmacology. Antonie van Leeuwenhoek 2000; 77: 135-145.

Faulkner DJ. Marine natural products. Natural Product Reports 2001; 18: 1R-49R.

Faulkner DJ. Highlights of marine natural products chemistry (1972-1999). Natural Product Reports 2000; 17: 1-6.

Ireland CM, Copp BR, Foster MP, et al. Biomedical potential of marine natural products. In: Pharmaceutical and Bioactive Natural Products. Springer 1993; pp. 1-43.

Haefner B. Drugs from the deep: marine natural products as drug candidates. Drug Discovery Today 2003; 8: 536-544.

Mayer AM, Glaser KB, Cuevas C, et al. The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends in Pharmacological Sciences 2010; 31: 255-265.

Andavan GSB, Lemmens-Gruber R. Cyclodepsipeptides from marine sponges: Natural agents for drug research. Marine Drugs 2010; 8: 810-834.

Miller JH, Singh AJ, Northcote PT. Microtubule-stabilizing drugs from marine sponges: focus on peloruside A and zampanolide. Marine Drugs 2010; 8: 1059-1079.

Monks NR, Lerner C, Henriques AT, et al. Anticancer, antichemotactic and antimicrobial activities of marine sponges collected off the coast of Santa Catarina, southern Brazil. Journal of Experimental Marine Biology and Ecology 2002; 281: 1-12.

Kinghorn A, Farnsworth N, Soejarto D, et al. Novel strategies for the discovery of plant-derived anticancer agents. Pharmaceutical Biology 2003; 41: 53-67.

Catovsky D, Fooks J, Richards S. Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. British Journal of Haematology 1989; 72: 141-149.

Reed JC. Molecular biology of chronic lymphocytic leukemia: implications for therapy. In: Seminars in Hematology 1998. p. 3.

Rassenti LZ, Jain S, Keating MJ, et al. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood 2008; 112: 1923-1930.

Simon H-U, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000; 5: 415-418.

Kiss T. Apoptosis and its functional significance in molluscs. Apoptosis 2010; 15: 313-321.

Newmeyer DD, Farschon DM, Reed JC. Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. Cell 1994; 79: 353-364.

Liu X, Kim CN, Yang J, et al. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996; 86: 147-157.

Hosseini M-J, Shaki F, Ghazi-Khansari M, Pourahmad J. Toxicity of vanadium on isolated rat liver mitochondria: a new mechanistic approach. Metallomics 2013; 5: 152-166.

Salimi A, Roudkenar MH, Sadeghi L, et al. Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria. Redox Biology 2015; 6: 461-471.

Rotem R, Heyfets A, Fingrut O, et al. Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Research 2005; 65: 1984-1993.

Blattner JR, He L, Lemasters JJ. Screening assays for the mitochondrial permeability transition using a fluorescence multiwell plate reader. Analytical biochemistry 2001; 295: 220-226.

Faizi M, Salimi A, Rasoulzadeh M, et al. Schizophrenia induces oxidative stress and cytochrome C release in isolated rat brain mitochondria: a possible pathway for induction of apoptosis and neurodegeneration. Iranian journal of pharmaceutical research: IJPR 2014; 13: 93.

Rezaei M, Salimi A, Taghidust M, et al. A comparison of toxicity mechanisms of dust storm particles collected in the southwest of Iran on lung and skin using isolated mitochondria. Toxicological & Environmental Chemistry 2014; 96: 814-830.

Salimi A, Ayatollahi A, Seydi E, et al. Direct toxicity of amyloid beta peptide on rat brain mitochondria: preventive role of Mangifera indica and Juglans regia. Toxicological & Environmental Chemistry 2015: 1-14.

Pirahmadi N, Fazeli M, Zarghi A, et al. 4-(4-(Methylsulfonyl) phenyl)-3-phenoxy-1-phenylazetidin-2-one: a novel COX-2 inhibitor acting selectively and directly on cancerous B-lymphocyte mitochondria. Toxicological & Environmental Chemistry 2015; 97: 908-921.

Mendola D. Aquacultural production of bryostatin 1 and ecteinascidin 743. Karger: Basel 2000.

Raj L, Ide T, Gurkar AU, et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 2011; 475: 231-234.

Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Molecular Cell 2012; 48: 158-167.

Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature reviews Drug Discovery 2009; 8: 579-591.

Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004; 305: 626-629.

Belzacq A-S, El Hamel C, Vieira H, et al. Adenine nucleotide translocator mediates the mitochondrial membrane permeabilization induced by lonidamine, arsenite and CD437. Oncogene 2001; 20: 7579-7587.

Brenner C, Grimm S. The permeability transition pore complex in cancer cell death. Oncogene 2006; 25: 4744-4756.

Brenner C, Le Bras M, Kroemer G. Insights into the mitochondrial signaling pathway: what lessons for chemotherapy? Journal of Clinical Immunology 2003; 23: 73-80.

Debatin K-M. Apoptosis pathways in cancer and cancer therapy. Cancer Immunology, Immunotherapy 2004; 53: 153-159.

Byrne AM, Lemasters JJ, Nieminen AL. Contribution of increased mitochondrial free Ca2+ to the mitochondrial permeability transition induced by tert‐butylhydroperoxide in rat hepatocytes. Hepatology 1999; 29: 1523-1531.

Maciel EN, Vercesi AE, Castilho RF. Oxidative stress in Ca2+‐induced membrane permeability transition in brain mitochondria. Journal of Neurochemistry 2001; 79: 1237-1245.

Zamzami N, Hirsch T, Dallaporta B, et al. Mitochondrial implication in accidental and programmed cell death: apoptosis and necrosis. Journal of Bioenergetics and Biomembranes 1997; 29: 185-193.

Zhao K, Zhao G-M, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. Journal of Biological Chemistry 2004; 279: 34682-34690.

Desagher S, Martinou J-C. Mitochondria as the central control point of apoptosis. Trends in Cell Biology 2000; 10: 369-377.




How to Cite

Ahmad Salimi, Mehrnoush Pir Saharkhiz, Abbasali Motallebi, Enayatollah Seydi, Ali Reza Mohseni, Melika Nazemi, & Jalal Pourahmad. (2015). Standardized Extract of the Persian Gulf Sponge, Axinella Sinoxea Selectively Induces Apoptosis through Mitochondria in Human Chronic Lymphocytic Leukemia Cells. Journal of Analytical Oncology, 4(4),  132–140.