Colorectal Cancer Cells

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The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.







Greenhough A, Patsos HA, Williams AC, Paraskeva C.

Source

Department of Cellular and Molecular Medicine, Cancer Research UK, Colorectal Tumour Biology Group, School of Medical Sciences, University of Bristol, University Walk, Bristol, United Kingdom.



Deregulation of cell survival pathways and resistance to apoptosis are widely accepted to be fundamental aspects of tumorigenesis. As in many tumours, the aberrant growth and survival of colorectal tumour cells is dependent upon a small number of highly activated signalling pathways, the inhibition of which elicits potent growth inhibitory or apoptotic responses in tumour cells. Accordingly, there is considerable interest in therapeutics that can modulate survival signalling pathways and target cancer cells for death. There is emerging evidence that cannabinoids, especially Delta(9)-tetrahydrocannabinol (THC), may represent novel anticancer agents, due to their ability to regulate signalling pathways critical for cell growth and survival. Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells. THC-induced apoptosis was rescued by pharmacological blockade of the CB1, but not CB2, cannabinoid receptor. Importantly, THC treatment resulted in CB1-mediated inhibition of both RAS-MAPK/ERK and PI3K-AKT survival signalling cascades; two key cell survival pathways frequently deregulated in colorectal tumours. The inhibition of ERK and AKT activity by THC was accompanied by activation of the proapoptotic BCL-2 family member BAD. Reduction of BAD protein exp<b></b>ression by RNA interference rescued colorectal cancer cells from THC-induced apoptosis. These data suggest an important role for CB1 receptors and BAD in the regulation of apoptosis in colorectal cancer cells. The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.



2007 Wiley-Liss, Inc.









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Colorectal cancer is cancer that forms in either the colon or the rectum. The colon and rectum are parts of the body's gastrointestinal (digestive) system. They form a long, muscular tube called the large intestine (or large bowel).



After food is chewed and swallowed, it travels down the esophagus to the stomach and then to the small intestine. From the small intestine, partly digested food enters the colon (the first five feet of the large intestine), which removes water and nutrients from the food and turns the rest into waste (stool). The waste then passes from the colon (which consists of four sections) into the rectum (the last six inches of the large intestine) and then out of the body.



Colorectal cancer can start in the tissues of any of the four sections of the colon or in the rectum. When cells that line either of these organs become abnormal and grow out of control, a cancerous tumor forms. In most cases, colorectal cancers develop slowly over a period of several years. Adenocarcinomas account for about 95 percent of colorectal cancers. Adenocarcinomas (e.g., mucinous, signet ring cell) begin in the intestinal gland cells that line the inside of the colon and rectum. My link Video





Symptoms

Many cases of colon cancer have no symptoms. The following symptoms, however, may indicate colon cancer:

• Abdominal pain and tenderness in the lower abdomen
  
• Blood in the stool
  
• Diarrhea, constipation, or other change in bowel habits
  
• Narrow stools
  
• Weight loss with no known reason
  

Signs and tests

With proper screening, colon cancer can be detected before symptoms develop, when it is most curable.



Your doctor will perform a physical exam and press on your belly area. The physical exam rarely shows any problems, although the doctor may feel a lump (mass) in the abdomen. A rectal exam may reveal a mass in patients with rectal cancer, but not colon cancer.



A fecal occult blood test (FOBT) may detect small amounts of blood in the stool, which could suggest colon cancer. However, this test is often negative in patients with colon cancer. For this reason, a FOBT must be done along with colonoscopy or sigmoidoscopy. It is also important to note that a positive FOBT doesn't necessarily mean you have cancer.



Imaging tests to screen for and potentially diagnose colorectal cancer include:

• Colonoscopy
  
• Sigmoidoscopy
  

Note: Only colonoscopy can see the entire colon, and this is the best screening test for colon cancer.



Blood tests that may be done include:

• Complete blood count (CBC) to check for anemia
  
• Liver function tests
  

Treatment



Treatment depends on many things, including the stage of the cancer. In general, treatments may include:



Surgery (most often a colectomy) to remove cancer cells



Chemotherapy to kill cancer cells



Radiation therapy to destroy cancerous tissue





Cancer of the colon or rectum is also called colorectal cancer. In the United States, it is the fourth most common cancer in men and women. Caught early, it is often curable.



It is more common in people over 50, and the risk increases with age. You are also more likely to get it if you have

• Polyps - growths inside the colon and rectum that may become cancerous
  
• A diet that is high in fat
  
• A family history or personal history of colorectal cancer
  
• Ulcerative colitis or Crohn's disease
  

Symptoms can include blood in the stool, narrower stools, a change in bowel habits and general stomach discomfort. However, you may not have symptoms at first, so screening is important. Everyone who is 50 or older should be screened for colorectal cancer. Colonoscopy is one method that your doctor can use to screen for colorectal cancer. Treatments for colorectal cancer include surgery, chemotherapy, radiation or a combination.



NIH: National Cancer Institute

The prognosis (chance of recovery) depends on the following:

• The stage of the cancer (whether the cancer is in the inner lining of the colon only, involves the whole colon, or has spread to other places in the body).
  
• Whether the cancer has blocked or created a hole in the colon.
  
• Whether there are any cancer cells left after surgery.
  
• The blood levels of carcinoembryonic antigen (CEA; a substance in the blood that may be increased when cancer is present) before treatment begins.
  
• Whether the cancer has recurred.
  
• The patients general health.
  

Treatment options depend on the following:

• The stage of the cancer.
  
• Whether the cancer has recurred.
  
• The patients general health.
  

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