Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

Related Experiment Video

Updated: Oct 2, 2026

Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
11:27

Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy

Published on: April 29, 2014

H Sasamura1, A Takahashi, N Miyao

  • 1Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.

British Journal of Cancer
|March 5, 2002
PubMed

Insights

Genistein effectively inhibits angiogenesis in renal cell carcinoma by suppressing key growth factors. This finding offers a promising new therapeutic avenue for this difficult-to-treat cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal cell carcinoma (RCC) often resists conventional treatments like chemotherapy and radiotherapy.
  • Angiogenesis, the formation of new blood vessels, is crucial for RCC growth and is a potential therapeutic target.
  • Identifying novel anti-angiogenic agents is essential for developing effective RCC therapies.

Purpose of the Study:

  • To evaluate the anti-angiogenic potential of five agents: medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochloride, and genistein.
  • To assess the inhibitory effects of these agents on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in RCC.
  • To investigate the mechanism by which genistein inhibits angiogenesis.

Main Methods:

  • Northern blot analysis was employed to quantify mRNA expression levels of VEGF and bFGF.
  • Five known anti-angiogenic agents were tested for their effects on VEGF and bFGF mRNA expression.
  • The impact of genistein on VEGF and bFGF mRNA expression was further examined under conditions of epidermal growth factor stimulation and hypoxia.

Main Results:

  • Genistein demonstrated a significant inhibitory effect on both VEGF and bFGF mRNA expression.
  • Medroxyprogesterone acetate and interferon-alpha showed no significant impact on VEGF or bFGF mRNA levels.
  • Interferon-gamma and minocycline exhibited mild inhibitory effects on VEGF and bFGF mRNA expression.
  • Genistein suppressed VEGF and bFGF mRNA expression even when induced by epidermal growth factor and hypoxia.

Conclusions:

  • Genistein is a potent inhibitor of angiogenesis in renal cell carcinoma.
  • Suppression of vascular endothelial growth factor and basic fibroblast growth factor expression is a key mechanism underlying genistein's anti-angiogenic activity.
  • Genistein represents a promising therapeutic candidate for renal cell carcinoma treatment.

Related Concept Videos

Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...