Report #15
Squalamine
& Squalene
Shark liver oil against cancer


What is squalamine?

Squalamine is an immune molecule found in the bodies of sharks that scientists are studying to see how it can help humans with diseases ranging from diabetes to cancer. It is a powerful
angiogenesis inhibitor, originally isolated from the liver of dogfish sharks.

What is
angiogenesis? From Wikipedia:


Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Angiogenesis is a normal process in growth and development, as well as in wound healing. However, this is also a fundamental step in the transition of tumors from a dormant state to a malignant state. An angiogenesis inhibitor is a drug, or a dietary component that inhibits angiogenesis (the growth of new blood vessels.)

From http://squalamine.com/:
Squalamine is not a protein. Instead, it is the first known example of a class of compounds called aminosterols, each a steroid chemically linked to an amino acid. And while proteins make poor drugs, because they are easily destroyed by digestive enzymes in the stomach, squalamine remains unscathed through the digestive tract. 

Squalamine has been investigated by Johns Hopkins School of Medicine researchers, Dr. Henry Brem, Dr. Allen Sills, Dr. Mark Donowitz and their collaborators for its tumor destroying ability. Squalamine destroyed the tumor spreading ability in rabbits by suppressing the growth of new blood vessels needed to support the growth of tumors. Squalamine halted the growth of brain tumors in rats and prolonged the lives of the laboratory animals. At the 1996 annual meeting of the American Association of Neurological Surgeons in Minneapolis, Dr. Brem commented, "Our findings present evidence that squalamine may work against brain cancer." Preliminary studies with certain brain cancer cells (glioma) have been encouraging.

The following statement has been published by The John Hopkins University in August, 1998.

From The Johns Hopkins Gazette:

Laboratory studies at Johns Hopkins have dramatically confirmed the power of a chemical discovered from the liver of sharks to slow the formation of new blood vessels destined to feed brain cancers as well as other tumors.

Squalamine, previously shown to have antibiotic and anti-cancer activity, inhibited the growth of brain cancers called gliomas implanted in the flanks of rats by disabling blood vessel growth, or angiogenesis, say the authors of the studies, published in the July 1 issue of the journal Cancer Research.

"Our results suggest that squalamine may be well suited for humans in the treatment of brain tumors and other diseases characterized by and dependent on new blood vessel growth," says Henry Brem, director of neurosurgical oncology at Hopkins and senior author of the study. "It dramatically slowed blood vessel formation without damaging healthy cells or embryonic development."

Named for the shark genus Squalus, squalamine was discovered in 1992 by scientists who founded Magainin Pharmaceuticals, which processes the chemical and funded the Hopkins studies. Squalamine is the first of a new class of naturally occurring molecules, aminosterols, under development for human therapies.

Squalamine is isolated from the tissues of the dog shark. It blocks or interferes with several steps in a cascade of events involved in blood vessel growth. Based on the Hopkins laboratory work, it is currently in Phase I clinical trials at the University of Texas (San Antonio) and at Georgetown Cancer Center.

Further statements from The Johns Hopkins Gazette:

Medical News

Shark-liver substance may slow brain tumors

Results of Hopkins animal studies show that a natural shark substance nearly stops the growth of new blood vessels that nourish solid brain tumors. The results suggest that the substance, squalamine, named for the shark genus Squalus, may find a role with chemotherapy, radiation and surgery in treating brain cancer and other solid tumors in people, say scientists from Hopkins and Magainin Pharmaceuticals, which processes squalamine and funded the studies.

Hopkins scientists added squalamine, a hormone-like chemical concentrated in the liver of the dogfish shark, and a growth factor to lab dishes containing central nervous system blood vessel cells from cows and squalamine alone to lab dishes containing human, rabbit or rat solid brain tumor cells. The blood vessel cells' rate of growth fell by up to 83 percent after two days, while the tumor cells treated with squalamine were unaffected. Results of a second study showed that time-release capsules containing squalamine slowed the growth of new blood vessels caused by tumors in rabbits' eyes by up to 43 percent after three weeks. Uncontrolled growth of blood vessels fuels the runaway cell growth of malignant tumors.

Other investigators also are exploring natural shark substances for use against human diseases, but this is believed to be the first evidence that squalamine may work against brain cancer. Squalus sharks' livers produce an oil used in manufacturing drugs, and small amounts of squalamine are found in shark cartilage. Squalamine dramatically slowed blood vessel cell growth without damaging healthy cells, according to Henry Brem, co-author of the studies and director of neurosurgical oncology, and Allen K. Sills, lead author and a Hopkins neurosurgery resident.


From CNN, July 1998:

NEW YORK (CNN) -- Sharks are generally thought of as killers, but one type may be a lifesaver.

The relatively gentle dog shark possesses squalamine, a naturally occurring cancer-fighting chemical that gives hope for cancer patients, said researchers from Johns Hopkins.

The hormone-like substance that can be isolated from the shark's liver and synthesized in a lab, can dramatically slow tumor growth without damaging healthy cells by stopping blood vessels from growing, said Dr. Henry Brem of Johns Hopkins Hospital.

Experiments in rats showed squalamine shrinks the deadliest form of brain cancer, glioblastoma.

All cancerous tumors require blood vessels to feed their cells, and squalamine may be able to starve them to death.

Writes Dr. Maras, MD (http://cancerchoices.com/) :

Fisherman of the Surga Bay on the Izu Peninsula of ancient Japan called it "Samedawa" or "cure all". The sharks they fished from the bottom of the bay measuring over 1000 meters deep, had a delectable meat. They specially valued its liver oil which they ingested regularly because they felt better whenever they took it.

In 1758, Swedish botanist Carolus Linnaeus discovered and claimed the great health and medicinal value of oil extracts from deep sea sharks such as the spiny dogfish. In the Micronesian Islands, a "miracle working" shark oil has been an age old remedy for various sickness and diseases as well as a familiar source of strength, stamina and virility. The historic health benefits of shark liver oil has always been a mainstay in Scandinavian folk medicine. 

In Norway and Sweden, shark liver oil was used traditionally by fishermen for healing wounds and irritations of the respiratory tract and alimentary canal. In China, the extract of deep sea shark has been recorded in the ancient pharmaceutical book "Honzukomuko". 

In Spain, ancient mariners regularly took "aceite de bacalao" or oil of the great fish. They claimed a greater resistance to colds and various other diseases because of it. Even in Ernest Hemingway's book, "The Old Man and the Sea" it says of the old man... "He also drank shark liver oil each day from the drum in the shack where many of the fishermen kept their gear....It was very good against all colds and grippes and it was good for the eyes."

In 1906, Dr. Mitsumaru Tsujimoto made an in depth research on shark liver oil, specifically that of the deep sea shark species; the "Squalidae Group", and discovered that an extremely great quantity of unsaturated hydrocarbons was contained in the liver oil of these deep sea sharks. He later called the oil "Squalene". Dr. Tsujimoto's brilliant discovery was not fully established until 1931 when Prof. Calour, a Nobel prize awardee at Zurich University, Switzerland certified that squalene shark liver oil is a lipoprotein, an unsaturated hydrocarbon with a chemical structure C30H50. This means simply that it mainly contains 30 carbon atoms and 50 hydrogen atoms. Dr. Calour in his study of the chemical behavior of this unsaturated hydrocarbon revealed that the compound is naturally lacking 12 hydrogen atoms in its original form for it to be stable (the stable compound is C30H62) and will "capture hydrogen atoms" from any source available to make it stable and saturated. The most abundant source of hydrogen is water &shyp; H20. (Our food contains much H20, body fluids and blood are mainly H20, body cells contain much water, the human body is actually 70% water). Theoretically, C30H50 (squalene) reacts with water (H20) this way: C30H50 + 6H20 &shyp; C30H62 + 302. By capturing the hydrogen molecules, 3 oxygen molecules from the water are released. This shows that squalene, through a natural reaction with water, is capable of providing oxygen essential for healthy metabolism. This basic scientific theory shown in the above formula should provide us an insight how squalene might work when present in our bodies.

Amazing discoveries continue to be made on shark liver oil. More careful scientific studies are being made to thoroughly examine its full composition and health benefits. In 1922, scientists isolated the therapeutically active component in shark liver oil called alkoxyglycerols.

Since the 1950's, this component has been studied clinically for its healing benefits in over 50 countries. Alkoxyglycerols (AKG's) in mothers milk, is the key substance which provides infants with natural protection and immunity against infection as it helps in the continued development of their immune system. There are 10 times more AKG's in mother's milk than in cow's milk. Science has proven that breast fed babies are more resistant to infection and diseases even all through life because of the more abundant ingestion of AKG's in their early physical development. This immune supportive nutrient, Alkoxyglycerols (AKG's) is the primary active component in shark liver oil. In fact, there are 1000 times more AKG's in shark liver oil than mother's milk. and human adults commensurately need 1000 times more AKG's than infants in the need for continuing boosting and enhancing ones immune system. 

In the 1990's Johns Hopkins University discovered another ingredient in shark liver oil, Squalamine, found to be effective against many yeast, fungus and bacterial infections, and especially offers promise to immune compromise persons such as AIDS and cancer patients. Shark liver oil may well contain the secret of improved health and longevity for mankind.

**********************************************

You may wonder, having read the report so far, what has happened in the field of squalamine research since 1998? After all, these fascinating results were obtained almost a decade ago! What happened with the Phase I clinical trials at the University of Texas (San Antonio) and at Georgetown Cancer Center?

The answer is simple; there is no mystery. All effective modalities that endanger the medical cash flow are suppressed, not only squalamine. Consider Insulin Potentiation Therapy, which is able to turn an extremely toxic treatment into a benign and much more effective therapy, using already approved substances (insulin and chemotherapeutic agents). There are no funds for IPT clinical trials, nor for trials involving any of the modalities described on this website. Squalamine simply joins the long line of suppressed treatments that the medical establishment doesn't want you to know about.

Despite the efforts of our medical leaders to block the medical use of this powerful but not patentable anti-cancer substance, squalamine as a marketable product has been researched and developed both in Japan and in New Zealand. Marketed under the names of Squalamax, Squalene, etc., it is available from several distributors in North America as an inexpensive dietary supplement. There has also been vigorous research into Squalamine's anti-cancer capabilities by scientists all over the world.
Here are some links to abstracts from scientists researching the medical use of Squalamine against cancer.

PubMed:

1 Chernova MN, Vandorpe DH, Clark JS, Williams JI, Zasloff MA, Jiang L, Alper SL.

Apparent receptor-mediated activation of Ca2+-dependent conductive Cl- transport by shark-derived polyaminosterols.
Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1644-58. Epub 2005 Aug 18.
PMID: 16109810 [PubMed - indexed for MEDLINE]
2: Pietras RJ, Weinberg OK.
Antiangiogenic Steroids in Human Cancer Therapy.
Evid Based Complement Alternat Med. 2005 Mar;2(1):49-57. Epub 2005 Feb 9.
PMID: 15841278 [PubMed - as supplied by publisher]
3: Bayes M, Rabasseda X, Prous JR.
Gateways to clinical trials.
Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612. Review.
PMID: 15538546 [PubMed - indexed for MEDLINE]
4: Sokoloff MH, Rinker-Schaeffer CW, Chung LW, Brendler CB.
Adjunctive therapy for men with high risk localized and locally advanced prostate cancer: targeting disseminated tumor cells.
J Urol. 2004 Dec;172(6 Pt 2):2539-44. Review.
PMID: 15538203 [PubMed - indexed for MEDLINE]
5: Choucair B, Dherbomez M, Roussakis C, El-kihel L.
Synthesis of 7 alpha- and 7 beta-spermidinylcholesterol, squalamine analogues.
Bioorg Med Chem Lett. 2004 Aug 16;14(16):4213-6.
PMID: 15261272 [PubMed - indexed for MEDLINE]
6: Cho J, Kim Y.
Sharks: a potential source of antiangiogenic factors and tumor treatments.
Mar Biotechnol (NY). 2002 Dec;4(6):521-5.
PMID: 14961226 [PubMed]
7: Sridhar SS, Shepherd FA.
Abstract Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer.
Lung Cancer. 2003 Dec;42 Suppl 1:S81-91. Review.
PMID: 14611919 [PubMed - indexed for MEDLINE]
8: Herbst RS, Hammond LA, Carbone DP, Tran HT, Holroyd KJ, Desai A, Williams JI, Bekele BN, Hait H, Allgood V, Solomon S, Schiller JH.
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. 2003 Sep 15;9(11):4108-15.
PMID: 14519633 [PubMed - indexed for MEDLINE]
9: Shepherd FA, Sridhar SS.
Angiogenesis inhibitors under study for the treatment of lung cancer.
Lung Cancer. 2003 Aug;41 Suppl 1:S63-72. Review.
PMID: 12867064 [PubMed - indexed for MEDLINE]
10: Hao D, Hammond LA, Eckhardt SG, Patnaik A, Takimoto CH, Schwartz GH, Goetz AD, Tolcher AW, McCreery HA, Mamun K, Williams JI, Holroyd KJ, Rowinsky EK.
A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor.
Clin Cancer Res. 2003 Jul;9(7):2465-71.
PMID: 12855619 [PubMed - indexed for MEDLINE]
11: 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.
PMID: 11973639 [PubMed - indexed for MEDLINE]
12: Shu Y, Jones SR, Kinney WA, Selinsky BS.
The synthesis of spermine analogs of the shark aminosterol squalamine.
Steroids. 2002 Mar;67(3-4):291-304.
PMID: 11856553 [PubMed - indexed for MEDLINE]
13: Bhargava P, Marshall JL, Dahut W, Rizvi N, Trocky N, Williams JI, Hait H, Song S, Holroyd KJ, Hawkins MJ.
A phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers.
Clin Cancer Res. 2001 Dec;7(12):3912-9.
PMID: 11751482 [PubMed - indexed for MEDLINE]
14: Marwick C.
Natural compounds show antiangiogenic activity.
J Natl Cancer Inst. 2001 Nov 21;93(22):1685. No abstract available.
PMID: 11717328 [PubMed - indexed for MEDLINE]
15: Williams JI, Weitman S, Gonzalez CM, Jundt CH, Marty J, Stringer SD, Holroyd KJ, Mclane MP, Chen Q, Zasloff M, Von Hoff DD.
Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.
Clin Cancer Res. 2001 Mar;7(3):724-33.
PMID: 11297269 [PubMed - indexed for MEDLINE]
16: Donowitz M, Janecki A, Akhter S, Cavet ME, Sanchez F, Lamprecht G, Zizak M, Kwon WL, Khurana S, Yun CH, Tse CM.
Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts.
Ann N Y Acad Sci. 2000;915:30-42. Review.
PMID: 11193592 [PubMed - indexed for MEDLINE]
17: 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. 1999 Dec;5(12):4287-94.
PMID: 10632372 [PubMed - indexed for MEDLINE]
18: Parker L.
Paediatric oncologists look forward to the millennium.
Lancet. 1999 Sep 25;354(9184):1100. No abstract available.
PMID: 10509510 [PubMed - indexed for MEDLINE]
19: 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. 1998 Jul-Aug;18(4A):2567-73.
PMID: 9703911 [PubMed - indexed for MEDLINE]
20: Sills AK Jr, Williams JI, Tyler BM, Epstein DS, Sipos EP, Davis JD, McLane MP, Pitchford S, Cheshire K, Gannon FH, Kinney WA, Chao TL, Donowitz M, Laterra J, Zasloff M, Brem H.
Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.
Cancer Res. 1998 Jul 1;58(13):2784-92.
PMID: 9661892 [PubMed - indexed for MEDLINE]

Science Daily article, July 7, 1998. In laboratory tests, squalamine proved to be as effective as the chemotherapeutic agent carmustine in slowing the growth of gliomas, the most common and deadly brain tumors, in rats. Carmustine has toxic side effects; squalamine has none.

From Georgetown University (
explore.georgetown.edu):
"In 1993, Dr. Zasloff and his group discovered squalamine in tissues of the dogfish shark, the first of a novel class of steroids, called aminosterols. Subsequently his group discovered squalamine to be a potent antiangiogenic compound with activity against solid tumors. Squalamine is currently in Phase II clinical trials being evaluated for treatment of non-small cell lung cancer and refractory ovarian cancer. "

From http://ajpcell.physiology.org/: Scientific paper
". . . squalamine has been shown to inhibit vascular endothelial growth factor-induced growth of endothelial cells, which do not contain NHE3 (16). Thus the specificity of squalamine, as currently recognized, is partially de-fined by cell type."

From Discovery Channell:
" . . studies included lung cancer, breast cancer, prostate cancer, ovarian cancer, and melanoma. Ultimately . . . squalamine might be used to control all of these cancers and, perhaps, many others."

The National Cancer Institute's definition of Squalamine:
  It prevents the growth of new blood vessels into a solid tumor.

From http://www.worldwidewords.org
"The compound is believed to act by preventing blood vessels in the human body from obeying commands from cancer cells to link to them, so starving them of the blood supply that is essential for growth."

Here is an excerpt from a scientific paper from California University:

PIETRAS, RICHARD J

CALIFORNIA, UNIVERSITY OF, LOS ANGELES
1999 OVARIAN CANCER RESEARCH PROGRAM
IDEA AWARD
$459,000.00

" . . . a newly synthesized compound called squalamine, is a chemical that was first isolated from tissues of the dogfish shark (scientific name, Squalus acanthias). Squalamine was found to be a potent inhibitor of the growth of blood vessel cells in preclinical studies of lung and brain cancers. In fact, squalamine has been tested in early phase I clinical trials with patients, and the chemical has been shown to be nontoxic and well-tolerated by human subjects. In our preliminary studies with human ovarian cancer cells in the laboratory, squalamine has been shown to have strong antitumor effects that result primarily from its ability to block the vascular action of several blood vessel growth factors including VEGF, LPA, and estrogen.

From Oncogene (2002):

"Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells . . ."

How does Squalamine compare with shark cartilage? Here is what Dr. Henry Brem,M.D., director of neorosurgical oncology at Hopkin’s, and one of the leading researchers of shark cartilage has to say: “ An inhibitor in the form of a protein, like shark cartilage, wouldn't make it through a patient's digestive system. The current available treatment couldn't possibly be a successful treatment. Squalamine, on the other hand, is a different story. It has proved to be non-toxic and a potent inhibitor of angiogenesis in animal models. It appears to be extraordinarily selective, halting only the growth of cells being stimulated by growth factors secreted by tumors. And, finally, it doesn't break down during digestion.”..Hopkin’s Medical News


What is the significance of Squalamine for the cancer patient?

Squalamine does not directly kill cancer cells. Instead, it inhibits selectively the growth of tumor blood vessels.


"Squalamine blocks the in growth of blood vessels into a tumor, and therefore, it block's the tumor's growth, not because it kills the tumor cells, but it simply cuts off their blood supply if you will"
Dr.Allen Sill, Johns Hopkins University

" A tumor without a network of blood vessel formation is like a car without wheels- it's not going anywhere!"
   Dr.Greg Dowless


Squalamine becomes vitally important when there is a fast growing tumor, blocking blood circulation or pressing on a vital organ. By stopping tumor growth, Squalamine permits a slow, gradual elimination of the tumor or tumors to take place. When a tumor is being destroyed, the immune system reacts by inflammation and swelling. This, in case of a brain tumor, can become a serious concern.

Trials with laboratory animals indicate that Squalamine is capable of passing the blood/brain barrier. This is not surprising, as we know that shark liver oil is a rich source of squalene and alkylglycerol (glycerol ether lipids or AKG). Alkylglycerols are not only capable of passing the blood/brain barrier, they are also able to open the barrier for other substances. This has been demonstrated beyond doubt.

Restricting tumor growth is also vitally important as a tool to prevent metastasis, as well as preventing the cancer from emerging again.

By now it must be clear that Squalamine is not a cancer cure. It is an important, perhaps vitally important component in a comprehensive integrative cancer therapy, in combination with other, carefully selected therapies.

Here are some distributors where Squalamine products can be purchased:

http://www.nznaturalhealth.com/product_8.html
http://www.nznaturalhealth.com/product_14.html
http://www.cancerchoices.com/
http://www.the7thfire.com/health_and_nutrition/Shark_Liver_Oil.html
http://www.vitacart.com/ --- put into the PRODUCT SEARCH field: squalene, then look for Mayumi (Japan) squalene caps
MASA SQUALENE Video about squalene
MAYUMI SQUALENE
New Zealand Squalene
Masa Squalene
Japanese Squalene
Medical Research Products
Dr. Maras



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