Prevention Of Angiogenesis


Cancer is a terrifying disease in which there is growth of abnormal tissue in the body, called a tumor. This tumor needs several nutrients as well as oxygen supply to grow and progress. For this purpose, it needs an extensive blood supply which can provide these nutrients. Therefore, wherever cancer develops, it builds a lot of blood vessels around it to provide itself with the things it needs to survive and grow. This process is known as angiogenesis.

Normal tissues build blood vessels by secreting specific polypeptides. Tumors can form these polypeptides including Vascular Endothelial Growth Factor (VEGF) and angiopoitins (APN). Secretion of these peptides results in disorganized formation of blood vessels, which provide oxygen and nutrients to the tumor.

Anti-Angiogenesis Therapy:

Drugs that prevent these blood vessels from forming are a new avenue of cancer treatment that is being explored. Such drugs have lower resistance as well as low toxicity as they are aimed at the tumor’s blood supply and not the tumor itself. When blood vessel formation falls, the tumor does not get enough oxygen and nutrients and hence its cells start to die. Judah Folkman was the first person who used anti-angiogenesis treatment options as anti-cancer therapy. After that, several such drugs were developed that are aimed at a tumor’s blood supply.

A new class of drugs being used as anti-angiogenesis factor is monoclonal antibodies like bevacizumab. These can increase life expectancy in some cases of cancer. Anti-angiogenesis therapy works best if it is combined with chemotherapy or radiotherapy. This is because research has shown that using anti-angiogenic agents alone is not highly beneficial; in combination, though, it can work pretty well.

How Does A Tumor Metastasize?

First of all, tumor cells start to grow in size. Then angiogenesis occurs to provide these rapidly growing cells with oxygen and nutrients. This happens when tumor cells secrete factors like VEGF and APN. Then, these tumor cells invade the tissues surrounding them. Some of them break form the whole clump of tumor tissue and enters into blood vessels or lymphatic vessels. From here, they reach different organs where they again cause angiogenesis to support themselves. In this way tumors can spread to distant regions.

When VEGF and APN are over-expressed, angiogenesis and tumor growth also increase.

Anti-Angiogenic Therapy May Depend On Tumor Environment:

Angiogenic factors like VEGF are secreted not only by the tumor but also by the surrounding host tissues. Therefore tumor microenvironment can affect the growth of a tumor. So any drug that is introduced should target the angiogenic factors secreted by both the tumor as well as the surrounding tissue. In this regard, natural remedies work very well as they can be given at low dose and affect different points in the angiogenesis pathway. In this way, they can be effective against a large variety of tumors.

Use Of Herbs As Anti-Angiogenic Factors:

The first anti-angiogenic herb used was named fumagillin, which is an antibiotic that is produced by a fungus. Some of the herbs that are known today to inhibit angiogenesis include Aloe barbadensis, Chemillia sinensis, ginger, garlic, aloe vera, liquiroce, resveratrol etc. Some herbs that specifically target VEGF are Angelica sinensis, Viscum album, Taxus brevifolia etc. These herbs are given continuously at low doses, so their adverse effects are less.

Some Specific Herbs:

  • Viscum album: Another name for this herb is Iscador. This herb down-regulates VEGF and causes tumor cell death. However, evidence in favor of this herb is not conclusive.
  • Artemisia annua: This derivative has been used as an anti-malarial. It also decreases new blood vessel formation as it inhibits the inner vessel lining, called endothelium, from forming.
  • Resveratrol: This is extracted from red grapes. This compound decreases VEGF production. It also affects other pathways including reduction in production of MMP-2, which is another factor needed for tumors to grow.
  • Silybum marianum: These are flavonoids which act against a lot of factors that cause tumor growth. They have been shown to be effective against ovarian cancers.
  • Quercetin: This flavonoid is present in several fruits including apples and citrus fruit. This affects several pathways including VEGF production, COX – 2, Lipoxygenase – 5 enzymes etc. All of these pathways are involved in angiogenesis and hence inhibiting them will limit tumor growth.
  • Camellia: These herbs are effective against angiogenesis produced by breast cancer. They affect angiogenesis at many different levels; hence their anti-tumor effects are wide-spread. Camellia is found in green tea which is why green tea is considered very good for health, particularly as an anti-tumor agent. This compound has been studied in rodents as well as in humans, with promising results.

Anti-Copper Agents:

Copper is required for different steps of blood vessel formation. Herbs that act as copper antagonists, therefore, can reduce angiogenesis by tumors. These include Caryophylli flos and Cinnamomi cortex.

Products Derived From Animals:

Tumors do not form in cartilage because they do not allow blood vessels formation. Derivatives from shark cartilage are thus being studied as anti-cancer agents. One of these products is AE-941, which not only inhibits angiogenesis but also decreases tumor formation in several other ways. These benefits have not yet been proven conclusively but research is ongoing.

Conclusion:

Anti-angiogenesis factors are highly beneficial in tumor suppression. Using natural herbs and products for this purpose is something that needs to be studied in greater detail. However, preliminary studies show promising results. The best thing is that these remedies are relatively safe and can be given along with chemotherapy to improve its cancer treating effects.

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