Marijuana Component Opens The Door For Virus That Causes Kaposi’s Sarcoma
The major active component of marijuana could enhance the ability of the virus that causes Kaposi’s sarcoma to infect cells and multiply, according to a team of researchers at Harvard Medical School. According to the researchers, low doses of delta-9-tetrahydrocannabinol (THC), equivalent to that in the bloodstream of an average marijuana smoker, could be enough to facilitate infection of skin cells and could even coax these cells into malignancy.
While most people are not at risk from Kaposi’s sarcoma herpes virus (KSHV), researchers say those with lowered immune systems, such as AIDS patients or transplant recipients, are more susceptible to developing the sarcoma as a result of infection. Their findings, reported in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, offer cautionary evidence that those with weakened immune systems should speak with their doctors before using marijuana medicinally or recreationally.
“These findings raise some serious questions about using marijuana, in any form, if you have a weakened immune system,” said lead study author Jerome E. Groopman, M.D., professor of medicine at Harvard Medical School. “While THC is best known as the main psychotropic part of marijuana, an analog of THC is the active ingredient of marinol, a drug frequently given to AIDS patients, among others, for increasing appetite and limiting chemotherapy-induced nausea and vomiting.”
While previous studies indicated that marijuana smoking was associated with Kaposi’s sarcoma, this is the first to demonstrate that THC itself can assist the virus in entering endothelial cells, which comprise skin and related tissue.
According to Dr. Groopman, the study illustrates the complicated role marijuana and other cannabinoids play in human health. Numerous types of cells display cannabinoid receptors on their outer surfaces, which act as switches that control cellular processes. Dr. Groopman’s laboratory had previously demonstrated that THC could have a protective effect against a certain form of invasive, drug-resistant lung cancer.
To study the combined effect of THC and KSHV, the researchers examined a culture of human skin cells, which are susceptible to infection and could provide a model of Kaposi’s sarcoma. These culture cells display many copies of two prominent cannabinoid receptors. Dr. Groopman and his colleagues found that by bonding to these receptors, low doses of THC activate two proteins responsible for maintaining a cell’s internal framework, or cytoskeleton.
By altering the cytoskeleton, THC effectively opens the door for KSHV, allowing the virus to more easily enter and infect the cell. “We can take away that effect by using antagonists that block the two cannabinoid receptors, which adds evidence that THC is the culprit,” Dr. Groopman said.
Once a cell is infected, the presence of THC may also promote the cellular events that turn it cancerous, the researchers say. They found that THC also promotes the production of a viral receptor similar to one that attracts a cell-signaling protein called interleukin-8. Previous studies have noted that this receptor could trigger the cell to reproduce, causing Kaposi’s sarcoma-like lesions in mice. Indeed, the researchers saw that THC induced the infected cells to reproduce and form colonies in culture.
“Here we see both infection and malignancy going on in the presence of THC, offering some serious concerns about the safety of THC among those at risk,” Dr. Groopman said. “Of course, we still do not know the exact molecular events that are occurring here, but these results are just the first part of our ongoing research.”
Cancer Res. 2007 Aug 1;67(15):7230-7.
Cannabinoid Modulation of Kaposi’s Sarcoma Associated Herpesvirus Infection and Transformation.
Zhang X, Wang JF, Kunos G, Groopman JE.
Division of Experimental Medicine and Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts and National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland.
Kaposi’s sarcoma-associated herpesvirus (KSHV; also named human herpesvirus 8 ) is necessary but not sufficient for the development of Kaposi’s sarcoma. A variety of factors may contribute to the pathogenesis of Kaposi’s sarcoma in addition to KSHV. Marijuana is a widely used recreational agent, and Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major active component of marijuana, is prescribed for medicinal use. To evaluate how cannabinoids may affect the pathogenesis of Kaposi’s sarcoma, we studied primary human dermal microvascular endothelial cells (HMVEC) exposed to KSHV. There was an increased efficiency of KSHV infection in the presence of low doses of Delta(9)-THC. We also found that Delta(9)-THC increased the viral load in KSHV-infected HMVEC through activation of the KSHV lytic switch gene, the open reading frame 50. Furthermore, we observed that Delta(9)-THC stimulated expression of the KSHV-encoded viral G protein-coupled receptor and Kaposi’s sarcoma cell proliferation. Our results indicate that Delta(9)-THC can enhance KSHV infection and replication and foster KSHV-mediated endothelial transformation. Thus, use of cannabinoids may place individuals at greater risk for the development and progression of Kaposi’s sarcoma. [Cancer Res 2007;67(15):7230-7].
PMID: 17671191 [PubMed – in process]