First some background: Brain cancer refers to the uncontrolled growth of cells in the brain, mainly neurons or glial cells. Glial cells refer to brain cells which do not actually conduct the signals that give rise to bodily function, but rather play a supportive role for neurons. When cancer arises from glial cells, such as oligodendrocytes, astrocytes, microglia, and ependyma, the tumor is referred to as a glioma. Malignant gliomas are the most prominent form of life-threatening brain cancer as well as one of the most aggressive forms of cancer known; thus although gliomas are not the most common, they are one of the most deadly cancers. Additionally, unlike lung or colon cancer, there are no known environmental factors that may cause brain cancer besides vinyl chloride or radiation, which the average person is not readily exposed to; and diagnosing brain cancer involves more expensive imaging techniques. These factors combined make gliomas one of the hardest forms of cancer to battle.
The new information: This experiment aimed to elucidate changes in cannabinoid receptor expression of gliomas. It was conducted by introducing antibodies raised against the receptors to human glial tumors and measuring the rate and levels at which the antibodies bound both cannabinoid receptor 1 and 2 (CB1 and CB2). It was found that in glioblastoma multiforme (the typical glioma), levels of CB1 were decreased by 43% and levels of CB2 were increased by 765% compared to a sample of normal, healthy brain tissue.
What this means: By altering levels of cannabinoid receptors, the brain cancer cells now differentiate themselves in terms of their response to cannabinoids. It has been widely documented that cannabinoids may induce cell apoptosis via CB2 receptors, and thus this astounding increase in CB2 receptor expression by gliomas make them far more susceptible to programmed cell death than other brain cells. Thus, levels of cannabinoids that would be safe for normal brain tissue would cause death in brain cancer cells. Therefore, cannabis may have potential therapeutic effects for those diagnosed with brain cancer, and more specifically, glioblastoma multiforme (GBM).
De Jesús, M.L., et al. “Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas.” Neurochemistry International. 56.6-7(2010): 829-33.
Showing posts with label cancer. Show all posts
Showing posts with label cancer. Show all posts
Wednesday, May 5, 2010
Sunday, April 11, 2010
June 2010: Cannabinoids inhibit a group of cancer-causing enzymes. (Hokuriku University; Kanazawa, Japan)
Note: June refers to the publication date
First some background: The human body contains an expansive number of enzymes, proteins which increase the rate of chemical reactions in our bodies. These enzymes typically facilitate the various molecular metabolic processes that are occurring at any given second within our cells, but some of their products and/or byproducts can be harmful, even carcinogenic (cause cancer). Perhaps the largest group of enzymes in our bodies is the cytochrome P450 (CYP) family, which catalyze the monooxidation (addition of one oxygen) of various organic molecules. One of the main functions of this enzyme family is the metabolism of drugs in the liver. However, some subfamilies, such as the CYP1 subfamily (enzymes CYP1A1, CYP1A2, CYP1B1), also induce the formation of carcinogenic compounds from polycyclic aromatic hydrocarbons. Polycyclic aromatic hydrocarbons are common constituents of smoke, especially cigarette smoke, and are known as procarcinogens. The label procarcinogen indicates that the molecule in and of itself will not cause cancer, but can be induced to cause cancer when altered by a metabolic process.
The new information: This experiment tested the effects of three cannabinoids found in marijuana on the catalytic effects of CYP1 enzymes. The three cannabinoids used were delta(9)-tetrahydrocannabinol (THC), cannabidiol, and cannabinol; it was found that all three cannabinoids inhibited all three CYP1 enzymes to some degree, with THC being the least potent inhibitor, cannabidiol inhibiting CYP1A1 most effectively, and cannabinol inhibiting CYP1A2 and CYP1B1 most effectively. Additionally, it was shown that all three cannabinoids were competitive inhibitors, meaning that at higher concentrations/potencies of other substrates for the CYP1 enzymes, the cannabinoids were displaced.
What this means: By illustrating that three of the major cannabinoids found in marijuana can cause potent inhibition of all three enzymes in the CYP1 subfamily, marijuana may prevent certain forms of cancer. Polycyclic aromatic hydrocarbons are common components in environmental pollution, and are usually inhaled, resulting in lung cancer. By inhibiting the enzyme that converts the procarcinogen into the cancer-causing compound, cannabis may be prophylactically used to prevent one of the main causes of lung cancer. Additionally, because CYP1 enzymes are also involved in drug metabolism, cannabis could be use to augment various pharmaceuticals for maximal effectiveness. In order for a drug to be excreted from the body, it generally first passes through at least two phases of metabolism, with cytochrome P450 enzymes representing one of the major components of the first phase. Thus if a drug is known to be metabolized by one of the CYP1 enzymes and cannabis is co-administered, it would take longer for the drug to be broken down in and removed from our bodies. Therefore, cannabis could extend the half-life of various medications, possibly reducing the cost to patients.
Yamaori, S., et al. “Characterization of Major Phytocannabinoids, Cannabidiol and Cannabinol, as Isoform-selective and Potent Inhibitors of Human CYP1 Enzymes.” Biochemical Pharmacology. 79.11(2010): 1691-8.
First some background: The human body contains an expansive number of enzymes, proteins which increase the rate of chemical reactions in our bodies. These enzymes typically facilitate the various molecular metabolic processes that are occurring at any given second within our cells, but some of their products and/or byproducts can be harmful, even carcinogenic (cause cancer). Perhaps the largest group of enzymes in our bodies is the cytochrome P450 (CYP) family, which catalyze the monooxidation (addition of one oxygen) of various organic molecules. One of the main functions of this enzyme family is the metabolism of drugs in the liver. However, some subfamilies, such as the CYP1 subfamily (enzymes CYP1A1, CYP1A2, CYP1B1), also induce the formation of carcinogenic compounds from polycyclic aromatic hydrocarbons. Polycyclic aromatic hydrocarbons are common constituents of smoke, especially cigarette smoke, and are known as procarcinogens. The label procarcinogen indicates that the molecule in and of itself will not cause cancer, but can be induced to cause cancer when altered by a metabolic process.
The new information: This experiment tested the effects of three cannabinoids found in marijuana on the catalytic effects of CYP1 enzymes. The three cannabinoids used were delta(9)-tetrahydrocannabinol (THC), cannabidiol, and cannabinol; it was found that all three cannabinoids inhibited all three CYP1 enzymes to some degree, with THC being the least potent inhibitor, cannabidiol inhibiting CYP1A1 most effectively, and cannabinol inhibiting CYP1A2 and CYP1B1 most effectively. Additionally, it was shown that all three cannabinoids were competitive inhibitors, meaning that at higher concentrations/potencies of other substrates for the CYP1 enzymes, the cannabinoids were displaced.
What this means: By illustrating that three of the major cannabinoids found in marijuana can cause potent inhibition of all three enzymes in the CYP1 subfamily, marijuana may prevent certain forms of cancer. Polycyclic aromatic hydrocarbons are common components in environmental pollution, and are usually inhaled, resulting in lung cancer. By inhibiting the enzyme that converts the procarcinogen into the cancer-causing compound, cannabis may be prophylactically used to prevent one of the main causes of lung cancer. Additionally, because CYP1 enzymes are also involved in drug metabolism, cannabis could be use to augment various pharmaceuticals for maximal effectiveness. In order for a drug to be excreted from the body, it generally first passes through at least two phases of metabolism, with cytochrome P450 enzymes representing one of the major components of the first phase. Thus if a drug is known to be metabolized by one of the CYP1 enzymes and cannabis is co-administered, it would take longer for the drug to be broken down in and removed from our bodies. Therefore, cannabis could extend the half-life of various medications, possibly reducing the cost to patients.
Yamaori, S., et al. “Characterization of Major Phytocannabinoids, Cannabidiol and Cannabinol, as Isoform-selective and Potent Inhibitors of Human CYP1 Enzymes.” Biochemical Pharmacology. 79.11(2010): 1691-8.
Wednesday, March 3, 2010
February 2010: Cannabinoids inhibit pain and bone loss induced by bone cancer (The University of Arizona; Tucson, Arizona)
First some background: Malignant bone cancer refers to a number of diverse tumor types, including osteosarcoma, chondrosarcoma, fibrosarcoma, cordoma, and Erwig’s sarcoma. Although the physiological mechanisms leading to tumor formation and malignancy may differ, the main symptoms of most forms of bone cancer are severe pain and bone loss. Thus, in standard treatment regiments for bone cancer, opiates are used in addition to chemotherapy and radiotherapy to abate the pain. However, use of opiates for analgesia has several downsides: physical addiction, high abuse potential, and rapid tolerance to name a few. Additionally, two side effects of chronic opiate use lead to an exacerbation of bone cancer symptoms. The first is pain hypersensitization. When the body is exposed to constant levels of any drug that acts as a receptor agonist, it induces a protective response to maintain its original state. Therefore when exposed to chronic opiate medications, the body reduces expression of opioid receptors, leading to decreased pain inhibition and thus increased sensitivity to pain. The second is hypogonadism. Opiates act on what is known as the hypothalamic-pituitary axis, causing decreased levels of hormone release. One of these hormones is GnRH (gonadotropin releasing hormone). GnRH causes release of two hormones from the anterior pituitary: LH (luteinizing hormone) and FSH (follicle stimulating hormone). These two hormones are responsible for regulating the amount of testosterone in both males and females. Although testosterone is widely known for being the main sex hormone in males, it is also present in lesser amounts in females with a common protective function of maintaining bone density. Thus chronic use of opiate medications will lead to an increased level of bone loss.
The new information: Cannabinoids have been shown to be a more valid alternative for treating bone cancer-mediated pain. The experiment was carried out by inducing bone cancer in mice and performing both behavioral and radiologic image interpretation of symptoms. After confirming the development of cancer, the mice were shown to have experienced both spontaneous and touch-evoked behavioral signs of pain. By administrating cannabinoids to the mice, both the spontaneous and stimulated pain was inhibited. Additionally, a sustained treatment regimen of cannabinoids led to significant reductions in bone loss, manifesting as a decreased likelihood of cancer-induced bone fractures.
What this means: By showing the benefits of utilizing cannabinoids as an alternative analgesic for bone cancer patients, cannabis may be a healthier alternative than opiates in treating pain associated with the cancer. Chronic use of opiates can cause more harm than good, as they often exacerbate the symptoms of bone cancer via patient hypersensitivity to pain and decreased bone mineral density. Cannabinoids on the other hand not only provide a non-physically addictive alternative, but also have been shown to attenuate the bone loss seen in cancer patients.
Lozano, A., et al. “A Cannabinoid 2 Receptor Agonist Attenuates Bone Cancer-induced Pain and Bone Loss.” Life Sciences. 2010: (preprint)
The new information: Cannabinoids have been shown to be a more valid alternative for treating bone cancer-mediated pain. The experiment was carried out by inducing bone cancer in mice and performing both behavioral and radiologic image interpretation of symptoms. After confirming the development of cancer, the mice were shown to have experienced both spontaneous and touch-evoked behavioral signs of pain. By administrating cannabinoids to the mice, both the spontaneous and stimulated pain was inhibited. Additionally, a sustained treatment regimen of cannabinoids led to significant reductions in bone loss, manifesting as a decreased likelihood of cancer-induced bone fractures.
What this means: By showing the benefits of utilizing cannabinoids as an alternative analgesic for bone cancer patients, cannabis may be a healthier alternative than opiates in treating pain associated with the cancer. Chronic use of opiates can cause more harm than good, as they often exacerbate the symptoms of bone cancer via patient hypersensitivity to pain and decreased bone mineral density. Cannabinoids on the other hand not only provide a non-physically addictive alternative, but also have been shown to attenuate the bone loss seen in cancer patients.
Lozano, A., et al. “A Cannabinoid 2 Receptor Agonist Attenuates Bone Cancer-induced Pain and Bone Loss.” Life Sciences. 2010: (preprint)
Thursday, February 18, 2010
February 2010: Cannabinoids sensitize cancer cells to lethal signals. (Universita di Palermo; Palermo, Italy)
First some background: According to the American Cancer Society, in 2009, approximately 22,620 cases of hepatic (liver) cancer were diagnosed, with an approximate 82% mortality rate. Although this is a relatively rare form of cancer, it can be caused by hepatitis or excessive alcohol consumption, and has one of the highest mortality rates. Hepatic cancer is one of the hardest cancers to diagnose, and according to the National Cancer Institute, approximately only 10-20% of liver tumors can be fully removed during surgery. If not removed, liver cancer it is usually deadly within three to six months. One of the molecular causes of cancer is known to be decreased apoptotic ability. Apoptosis refers to programmed cell death, in which a cell receives a specific signal, activating “suicidal” pathways that eventually terminate in the cell’s death. This process is used to control the proliferation of cells in our bodies, allowing us to keep a relatively constant numbers of each cell type. If a cell undergoes a mutation that leads to an inability to perform apoptosis, cell growth can no longer be controlled and a tumor is formed. If the cells within this tumor are capable of recruiting blood vessels and traveling to other parts of the body, they are referred to as malignant tumors, causing what is commonly known as cancer.
The new information: When cannabinoids were administered to human hepatocellular carcinoma (HHC) cells, it caused an up-regulation of a receptor known as DR5 (Death Receptor 5). This receptor allows binding of molecules known as TNFs (Tumor Necrosis Factors), and leads to the activation of an apoptotic pathway. When the DR5 receptors are up-regulated, there are more binding sites for TNFs, which leads to higher levels of cell death. Additionally, administration of the cannabinoid lead to a significant decrease in survival factors, which have the ability to halt the process of apoptosis. The cannabinoid in this study was co-administered with TRAIL (TNF-related apoptosis inducing ligand), leading to a significantly higher level of apoptosis than administration with TRAIL alone.
What this means: This illustrates a novel treatment for liver cancer; because it is one of the hardest carcinomas to remove surgically and its high mortality rate, liver cancer remains one of the deadliest forms. This study proved that administration of cannabinoids lead to an increased sensitivity of hepatic cancer cells to factors that lead to their death. Therefore, co-administration of cannabis with current cancer treatments can lead to an increase in their effectiveness.
Pellerito, O., et al. “The synthetic cannabinoid WIN sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis by activating p8/CHOP/DR5 axis.” Molecular Pharmacology. (2010): preprint.
The new information: When cannabinoids were administered to human hepatocellular carcinoma (HHC) cells, it caused an up-regulation of a receptor known as DR5 (Death Receptor 5). This receptor allows binding of molecules known as TNFs (Tumor Necrosis Factors), and leads to the activation of an apoptotic pathway. When the DR5 receptors are up-regulated, there are more binding sites for TNFs, which leads to higher levels of cell death. Additionally, administration of the cannabinoid lead to a significant decrease in survival factors, which have the ability to halt the process of apoptosis. The cannabinoid in this study was co-administered with TRAIL (TNF-related apoptosis inducing ligand), leading to a significantly higher level of apoptosis than administration with TRAIL alone.
What this means: This illustrates a novel treatment for liver cancer; because it is one of the hardest carcinomas to remove surgically and its high mortality rate, liver cancer remains one of the deadliest forms. This study proved that administration of cannabinoids lead to an increased sensitivity of hepatic cancer cells to factors that lead to their death. Therefore, co-administration of cannabis with current cancer treatments can lead to an increase in their effectiveness.
Pellerito, O., et al. “The synthetic cannabinoid WIN sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis by activating p8/CHOP/DR5 axis.” Molecular Pharmacology. (2010): preprint.
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