Squalamine has anticancer effects but definitive evidence is lacking.
Squalamine is an aminosterol derived from dogfish shark tissues. It has been shown to kill bacteria and block growth of new blood vessels in laboratory studies. Clinical trials show that squalamine is safe and well-tolerated when given to human subjects to treat cancer and age-related macular degeneration. However, most of these studies used the injectable form of squalamine. It is unclear if oral squalamine products have the same effects. Further studies are needed.
To treat cancer
Clinical studies have shown that the injectable form of squalamine is safe to give to human subjects with solid tumors, but they have not proven that squalamine is an effective anticancer drug.
To treat age-related macular degeneration
Clinical studies have shown that squalamine is safe to give to human subjects, but they have not proven that squalamine is an effective drug to treat the condition.
To treat bacterial infections
Experimental studies show that squalamine kills gram-positive and gram-negative bacteria, but clinical studies have not been done in humans to show that squalamine can be used to treat bacterial infections.
Do Not Take If
You are taking cisplatin, paclitaxel, and cyclophosphamide: Squalamine may increase cytotoxic effects.
You are taking colistin and tobramycin: Squalamine may increase antibiotic effects.
Squalamine is a water-soluble substance derived from the internal organs of dogfish, Squalus acanthias, and is thought to act as a systemic antimicrobial agent (1)(2). The oral form is marketed as a dietary supplement but the parenteral form has been used in clinical studies. Squalamine demonstrated significant bactericidal and fungicidal effects and also enhances the bactericidal effects when used in combination with standard antibiotics (3)(4).
Squalamine exhibits antiangiogenic property, and has been studied as a treatment for age-related macular degeneration and cancer. The injectable form is well tolerated in those with age-related macular degeneration and cancer in Phase I and II trials (5)(6)(7). However, it is unclear if oral squalamine has similar effects. Further studies are necessary.
Squalamine should not be confused with squalene, an oil found in shark liver.
Dogfish shark, Squalus acanthias: Squalamine is found primarily in liver and gallbladder, but also in the spleen, testes, stomach, gills, and intestine.
Sea lamprey, Petromyzon marinus
Age-related macular degeneration
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 an alteration in intracellular pH and a disruption of intracellular signaling induced by angiogenic growth factors (8).
Squalamine alters the shape and decreases 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 signaling pathways of VEGF, including VEGF-induced phosphorylation of p44/p42 MAP kinase in vascular endothelial cells (11), disrupts F-actin fibers, and induces internalization of vascular endothelial-cadherin from the membrane into the intracellular compartment (12). It decreases retinal neovascularization that is thought to benefit macular degeneration (17).
Squalamine is an amphipathic compound that interacts with various membrane glycerophospholipids at unique affinities (4). It has a faster killing rate of gram-positive bacteria than gram-negative bacteria (3)(13)(14).
Squalamine enhances the cytotoxicity of chemotherapy drugs (15) by promoting tumor cell apoptosis and by reduced angiogenesis (16)(10). Its antiangiogenic effects are due to inhibition of endothelial cell proliferation and migration induced by various growth factors (9).
In clinical studies using the parenteral form of squalamine, symptoms including fatigue, nausea, anorexia, and hepatotoxicity have been reported (9).
Cisplatin, paclitaxel, and cyclophosphamide: Squalamine may increase cytotoxic effects (6)(8)(10).
Colistin and tobramycin: Squalamine may increase antibiotic effects (13).