Squalamine

<a href="http://www.ncbi.nlm.nih.gov/pubmed/8433993" target="_blank">Squalamine: an aminosterol antibiotic from the shark.</a>

<a href="https://www.mskcc.org/cancer-care/integrative-medicine/herbs/squalamine">Per Sloan-Kettering</a>

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. Squalamine demonstrated significant bactericidal and fungicidal effects and also enhances the bactericidal effects when used in combination with standard antibiotics. 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.

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

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.

<h3>Mechanism of Action:</h3>

Squalamine is a cholestane steroid conjugated to a spermidine at position C-3. However, it does not have glucocorticoid and mineralocorticoid effects . 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 .

Squalamine alters the shape and decreases volume of endothelial cells in embryonic vascular beds, causing narrowing of the vessel lumen and occluding blood flow . 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 , disrupts F-actin fibers, and induces internalization of vascular endothelial cadherin from the membrane into the intracellular compartment . It decreases retinal neovascularization that is thought to benefit macular degeneration.

Squalamine is an amphipathic compound that interacts with various membrane glycerophospholipids at unique affinities . It has a faster killing rate of gram-positive bacteria than gram-negative bacteria .

Squalamine enhances the cytotoxicity of chemotherapy drugs by promoting tumor cell apoptosis and by reduced angiogenesis . Its antiangiogenic effects are due to inhibition of endothelial cell proliferation and migration induced by various growth factors.

You are taking cisplatin, paclitaxel, and cyclophosphamide: Squalamine may increase cytotoxic effects.
You are taking colistin and tobramycin: Squalamine may increase antibiotic effects.

<h3>Side Effects:</h3>

Liver toxicity
Nausea
Fatigue
Anorexia
Muscle weakness

<h3>Studies</h3>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/17726196" target="_blank">Identification of squalamine in the plasma membrane of white blood cells in the sea lamprey, Petromyzon marinus. </a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/20147322" target="_blank">Squalamine, an original chemosensitizer to combat antibiotic-resistant gram-negative bacteria.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/18648511" target="_blank">Squalamine: an appropriate strategy against the emergence of multidrug resistant gram-negative bacteria?</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/19668729" target="_blank">Current and emerging therapies for the treatment of age-related macular degeneration.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/14519633" target="_blank">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.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/12855619" target="_blank">A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/15841278" target="_blank">Antiangiogenic Steroids in Human Cancer Therapy.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/11751482" target="_blank">A phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/10632372" target="_blank">Potentiation of platinum antitumor effects in human lung tumor xenografts by the angiogenesis inhibitor squalamine: effects on tumor neovascularization</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/8621443" target="_blank">Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/11297269" target="_blank">Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/20335187" target="_blank">In vitro antifungal activity of aminosterols against moulds isolated from cystic fibrosis patients.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/19666647" target="_blank">In vitro antibacterial activity of aminosterols against multidrug-resistant bacteria from patients with cystic fibrosis</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/9703911" target="_blank">Potential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/11973639" target="_blank">Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression.</a>

<a href="http://www.ncbi.nlm.nih.gov/pubmed/10798670" target="_blank">Squalamine improves retinal neovascularization.</a>