Purported Benefits, Side Effects & More


Purported Benefits, Side Effects & More

Common Names

  • Squalamine lactate

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Squalamine may have anticancer effects, but definitive evidence is lacking.

Squalamine is a compound derived from dogfish shark tissues. Lab studies suggest it can kill bacteria and block growth of new blood vessels.

Small clinical studies suggest that squalamine is safe and well tolerated when given to patients with cancer and age-related macular degeneration. However, these studies used an injectable form, and it is unclear if oral squalamine products have the same effects. Further research is needed.

Squalamine should not be confused with squalene, an oil found in shark liver.

What are the potential uses and benefits?
  • To treat cancer

    Small clinical studies have shown that the injectable form of squalamine is safe in patients with solid tumors, but it is not known if it can treat cancer.
  • To treat age-related macular degeneration

    Small clinical studies suggest that squalamine is safe and well tolerated, but it is not known if it can be used to treat this condition.
  • To treat bacterial infections

    Squalamine showed antibacterial effects in lab studies, but clinical trials have not been conducted.
What are the side effects?
  • Fatigue, nausea, anorexia, and liver toxicity with intravenous squalamine in a clinical study.

For Healthcare Professionals

Clinical Summary

Squalamine is a water-soluble steroidal antibiotic first identified in dogfish shark (Squalus acanthias) tissue (1). It is now produced synthetically, and has significant bactericidal and fungicidal effects. It also enhances bactericidal effects when used in combination with standard antibiotics (2) (3) (4), and significantly reduces aggregation of alpha-synuclein, a protein associated with Parkinson’s disease and related syndromes (18).

Preclinical studies show that squalamine inhibits growth factor-dependent pathways in endothelial cells. It has been studied since as a treatment for age-related macular degeneration and cancer (19) (20), with the injectable form appearing to be well tolerated in early-phase trials (5) (6) (7). However, it is not known if oral squalamine would have similar effects.

Other preliminary findings suggest that topical squalamine along with ranibizumab improves visual recovery in patients with retinal vein occlusion-related macular edema (21), and a squalamine ointment demonstrated partial clinical activity against ringworm (22).

Squalamine analogues are currently being studied for nasal decolonization of Staphyloccus aureus to prevent risk of associated infections (23), and squalamine eye drops are being tested in the search for novel treatments of neovascular age-related macular degeneration (24).

Squalamine should not be confused with squalene, an oil found in shark liver.

Food Sources
  • Dogfish shark, Squalus acanthias: Squalamine is found primarily in the liver and gallbladder, but also the spleen, testes, stomach, gills, and intestine.
  • Sea lamprey, Petromyzon marinus  (2)
Purported Uses and Benefits
  • Cancer treatment
  • Age-related macular degeneration
  • Bacterial infections
Mechanism of Action

Squalamine is a cholestane steroid conjugated to a spermidine at position C-3. However, it does not have glucocorticoid and mineralocorticoid effects (8). Squalamine binds to cell membranes and inhibits the specific membrane Na+/H+ exchanger NHE3, causing intracellular pH alterations and disruption of intracellular signaling induced by angiogenic growth factors (8).

Squalamine alters shape and volume of endothelial cells in embryonic vascular beds, causing narrowing of the vessel lumen and occluding blood flow (10). These actions inhibit multiple key steps in angiogenesis, including mitogen-induced actin polymerization, cell-cell adhesion, and cell migration, ultimately inhibiting endothelial cell proliferation. Squalamine blocks downstream VEGF signaling pathways, including phosphorylation of p44/p42 MAP kinase in vascular endothelial cells (11). It also disrupts F-actin fibers and induces internalization of vascular endothelial-cadherin from the membrane into the intracellular compartment (12). It may also decrease retinal neovascularization that is thought to encourage macular degeneration (17).

Squalamine is an amphipathic compound that interacts with various membrane glycerophospholipids (4). It has a faster killing rate of gram-positive versus -negative bacteria (3) (13) (14). It also enhances chemotherapy drug cytotoxicity by promoting tumor cell apoptosis and reducing angiogenesis (10) (15) (16). Inhibition of growth factor-induced endothelial cell proliferation and migration contribute to antiangiogenic effects (9).

Adverse Reactions

Fatigue, nausea, anorexia, and hepatotoxicity with intravenous administration  (9)

  1. Moore KS, Wehrli S, Roder H, et al. Squalamine: an aminosterol antibiotic from the shark. Proc Natl Acad Sci U S A. Feb 15 1993;90(4):1354-1358.
  2. Yun SS, Li W. Identification of squalamine in the plasma membrane of white blood cells in the sea lamprey, Petromyzon marinus. J Lipid Res. Dec 2007;48(12):2579-2586.
  3. Lavigne JP, Brunel JM, Chevalier J, Pages JM. Squalamine, an original chemosensitizer to combat antibiotic-resistant gram-negative bacteria. J Antimicrob Chemother. Apr 2010;65(4):799-801.
  4. Salmi C, Loncle C, Vidal N, et al. Squalamine: an appropriate strategy against the emergence of multidrug resistant gram-negative bacteria? PLoS One. 2008;3(7):e2765.
  5. Emerson MV, Lauer AK. Current and emerging therapies for the treatment of age-related macular degeneration. Clin Ophthalmol. Jun 2008;2(2):377-388.
  6. Herbst RS, Hammond LA, Carbone DP, et al. A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res. Sep 15 2003;9(11):4108-4115.
  7. Hao D, Hammond LA, Eckhardt SG, et al. A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor. Clin Cancer Res. Jul 2003;9(7):2465-2471.
  8. Pietras RJ, Weinberg OK. Antiangiogenic Steroids in Human Cancer Therapy. Evid Based Complement Alternat Med. Mar 2005;2(1):49-57.
  9. Bhargava P, Marshall JL, Dahut W, et al. A phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers. Clin Cancer Res. Dec 2001;7(12):3912-3919.
  10. Schiller JH, Bittner G. Potentiation of platinum antitumor effects in human lung tumor xenografts by the angiogenesis inhibitor squalamine: effects on tumor neovascularization. Clin Cancer Res. Dec 1999;5(12):4287-4294.
  11. Soker S, Fidder H, Neufeld G, Klagsbrun M. Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain. J Biol Chem. Mar 8 1996;271(10):5761-5767.
  12. Williams JI, Weitman S, Gonzalez CM, et al. Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies. Clin Cancer Res. Mar 2001;7(3):724-733.
  13. Alhanout K, Brunel JM, Ranque S, Rolain JM. In vitro antifungal activity of aminosterols against moulds isolated from cystic fibrosis patients. J Antimicrob Chemother. Jun 2010;65(6):1307-1309.
  14. Alhanout K, Brunel JM, Raoult D, Rolain JM. In vitro antibacterial activity of aminosterols against multidrug-resistant bacteria from patients with cystic fibrosis. J Antimicrob Chemother. Oct 2009;64(4):810-814.
  15. Teicher BA, Williams JI, Takeuchi H, Ara G, Herbst RS, Buxton D. Potential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma. Anticancer Res. Jul-Aug 1998;18(4A):2567-2573.
  16. Li D, Williams JI, Pietras RJ. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression. Oncogene. Apr 25 2002;21(18):2805-2814.
  17. Higgins RD, Sanders RJ, Yan Y, Zasloff M, Williams JI. Squalamine improves retinal neovascularization. Invest Ophthalmol Vis Sci. May 2000;41(6):1507-1512.
  18. Perni M, Galvagnion C, Maltsev A, et al. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E1009-E1017.
  19. Genaidy M, Kazi AA, Peyman GA, et al. Effect of squalamine on iris neovascularization in monkeys. Retina. 2002 Dec;22(6):772-8.
  20. Li D, Williams JI, Pietras RJ. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression. Oncogene. 2002 Apr 25;21(18):2805-14.
  21. Wroblewski JJ, Hu AY. Topical Squalamine 0.2% and Intravitreal Ranibizumab 0.5 mg as Combination Therapy for Macular Edema Due to Branch and Central Retinal Vein Occlusion: An Open-Label, Randomized Study. Ophthalmic Surg Lasers Imaging Retina. 2016 Oct 1;47(10):914-923.
  22. Coulibaly O, Thera MA, Koné AK, et al. A double-blind randomized placebo-controlled clinical trial of squalamine ointment for tinea capitis treatment. Mycopathologia. 2015 Apr;179(3-4):187-93.
  23. Sakr A, Brégeon F, Rolain JM, Blin O. Staphylococcus aureus nasal decolonization strategies: a review. Expert Rev Anti Infect Ther. 2019 May;17(5):327-340.
  24. Pecen PE, Kaiser PK. Current phase 1/2 research for neovascular age-related macular degeneration. Curr Opin Ophthalmol. 2015 May;26(3):188-93.
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