Tag Archives: VEGF

Diindolylmethane & Ovarian cancer

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Ovarian cancer is a major cause of death worldwide. Approximately 25,000 women will be diagnosed with ovarian cancer this year and 15,000 women will die from it in the United States alone. The novel anti-cancer drug diindolylmethane (DIM) has been shown in laboratory to inhibit the growth of ovarian cancer cells. New research published in BioMed Central’s open access journal BMC Medicine has looked in detail at the action of DIM and showed that it works by blocking the activation and production of the transcription factor STAT3. DIM also enhances the anti-cancer effect of the platinum-based chemotherapy drug cisplatin.

Scientists from Texas Tech University Health Sciences Center, Amarillo already knew that DIM inhibited the growth of ovarian cancer cells but have now found that DIM causes ovarian cancer cell death (apoptosis). Not only was DIM able to kill cells but it also prevented cell invasion and angiogenesis, both of which are necessary for a cancer to grow.

STAT transcription factors are involved in the growth and survival of cells and are switched on by growth factors and immune system messengers (cytokines) such as IL-6. STAT3 is activated in 90% of ovarian cancers, however DIM was able to inhibit activation of STAT3 by preventing phosphorylation in response to IL-6. In a double whammy DIM also reduced the amount of IL-6 and the growth factor involved in angiogenesis (VEGF) in ovarian cancer cells.

Ovarian cancer

Ovarian cancer

Women with ovarian cancer are often treated with platinum containing chemotherapy drugs. However patients treated with cisplatin often relapse or fail to respond and cisplatin resistance is known to be associated with an increase in STAT3. In this study the combination of cisplatin and DIM suppressed tumour growth in mice by an extra 50% compared to cisplatin alone.


Prof Sanjay K. Srivastava and Prabodh K. Kandala who performed the research explained, “DIM increases the effect of cisplatin, without being toxic to normal ovarian cells, by targeting STAT3 signaling and increasing apoptosis. Cisplatin is very toxic and has severe side effects. If co-treatment with DIM means that a low dose of cisplatin can be given to patients without the loss of therapeutic effect, but with reduced side effects, it would represent a significant breakthrough in clinical practice.”

Tree compound fights cancer

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Researchers at Massachusetts General Hospital (MGH) have discovered an entirely new class of antiangiogenesis drugs – agents that interfere with the development of blood vessels- in a compound found in a South American tree.

They described how this compound called dehydro-alpha-lapachone (DAL), derived from Tabebuia avellanedae, a tree native to Argentina and Brazil, was able to help wound healing and inhibit tumor growth in animal models.

“Most of the FDA-approved antiangiogenesis drugs inhibit the pathway controlled by vascular endothelial growth factor or VEGF, which directly stimulates blood vessel development,” said Igor Garkavtsev, MD, PhD, of the Steele Laboratory for Tumor Biology at MGH and lead author of the study.

Garkavtsev and his colleagues first showed that DAL administration interfered with blood vessel formation in zebrafish, both during embryonic development and wound healing.

Tabebuia avellanedae

Tabebuia avellanedae

They then found that it reduced the vascular density of tumors implanted in mice and, with daily treatment, significantly reduced tumor growth with no signs of toxicity.

Experiments with endothelial cells from human umbilical veins revealed that DAL administration altered the size and shape of the cells by changing the organization of the actin cytoskeleton; blocked formation of new vascular networks and reorganized existing networks; and interfered with the movement of cells required for wound healing.


Further investigation found that DAL produces these effects by decreasing the activity of Rac1, a protein known to be important to cellular adhesion and cytoskeletal organization.

“DAL has the potential to improve treatment of many types of cancer and of other diseases characterized by abnormal blood vessels,” concluded Rakesh Jain, PhD, director of the Steele Lab and senior author of the study.

The finding was reported in Proceedings of the National Academy of Sciences/Early Edition.