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thc hcc
Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. When these tumors are in advanced stages, few therapeutic options are available. Therefore, it is essential to search for new treatments to fight this disease. In this study, we investigated the effects of cannabinoids--a novel family of potential anticancer agents--on the growth of HCC. We found that Δ(9)-tetrahydrocannabinol (Δ(9)-THC, the main active component of Cannabis sativa) and JWH-015 (a cannabinoid receptor 2 (CB(2)) cannabinoid receptor-selective agonist) reduced the viability of the human HCC cell lines HepG2 (human hepatocellular liver carcinoma cell line) and HuH-7 (hepatocellular carcinoma cells), an effect that relied on the stimulation of CB(2) receptor. We also found that Δ(9)-THC- and JWH-015-induced autophagy relies on tribbles homolog 3 (TRB3) upregulation, and subsequent inhibition of the serine-threonine kinase Akt/mammalian target of rapamycin C1 axis and adenosine monophosphate-activated kinase (AMPK) stimulation. Pharmacological and genetic inhibition of AMPK upstream kinases supported that calmodulin-activated kinase kinase β was responsible for cannabinoid-induced AMPK activation and autophagy. In vivo studies revealed that Δ(9)-THC and JWH-015 reduced the growth of HCC subcutaneous xenografts, an effect that was not evident when autophagy was genetically of pharmacologically inhibited in those tumors. Moreover, cannabinoids were also able to inhibit tumor growth and ascites in an orthotopic model of HCC xenograft. Our findings may contribute to the design of new therapeutic strategies for the management of HCC.
Endocannabinoids and liver disease
Liver International
Volume 25 Issue 5 Page 921 - October 2005
Ezra Gabbay1,2, Yosefa Avraham1, Yaron Ilan2, Eran Israeli and Elliot M. Berry1 1Department of Metabolism and Human Nutrition, Hadassah-Hebrew University Medical School, 2The Liver Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Abstract: Aims: Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease.
Methods: The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered.
Results: Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function.
Conclusions: Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities.
Liver International
Volume 25 Issue 5 Page 921 - October 2005
Ezra Gabbay1,2, Yosefa Avraham1, Yaron Ilan2, Eran Israeli and Elliot M. Berry1 1Department of Metabolism and Human Nutrition, Hadassah-Hebrew University Medical School, 2The Liver Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Abstract: Aims: Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease.
Methods: The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered.
Results: Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function.
Conclusions: Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities.
Marijuana may protect the immune system against HIV and slow disease progression
New evidence that chronic intake of THC, the primary psychoactive ingredient in marijuana, can protect critical immune tissue in the gut from the damaging effects of HIV infection is reported in AIDS Research and Human Retroviruses, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the AIDS Research and Human Retroviruses website.
Patricia Molina and coauthors from Louisiana State University Health Sciences Center, New Orleans, report that chronic THC administration was associated with greater survival of T cell populations and reduced overall cell death in the gut in monkeys, which is known to be a key target for simian immunodeficiency virus (HIV) replication and infection-related inflammation. The researchers present their findings in the article "Modulation of Gut-Specific Mechanisms by Chronic-9-Tetrahydrocannabinol Administration in Male Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Systems Biology Analysis." This report provides mechanistic insights into their previous observation that THC administration attenuates disease progression in SIV infected macaques (AIDS Research and Human Retroviruses 2011; 27: 585-592).
"To better treat HIV infection, we need a better understanding of how it causes the disease we call AIDS. We also need alternative approaches to treatment," says Thomas Hope, PhD, Editor-in-Chief of AIDS Research and Human Retroviruses and Professor of Cell and Molecular Biology at the Feinberg School of Medicine, Northwestern University, Chicago, IL. "This study is important because it begins to explain how THC can influence disease progression in SIV-infected macaques. It also reveals a new way to slow disease progression."
New evidence that chronic intake of THC, the primary psychoactive ingredient in marijuana, can protect critical immune tissue in the gut from the damaging effects of HIV infection is reported in AIDS Research and Human Retroviruses, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the AIDS Research and Human Retroviruses website.
Patricia Molina and coauthors from Louisiana State University Health Sciences Center, New Orleans, report that chronic THC administration was associated with greater survival of T cell populations and reduced overall cell death in the gut in monkeys, which is known to be a key target for simian immunodeficiency virus (HIV) replication and infection-related inflammation. The researchers present their findings in the article "Modulation of Gut-Specific Mechanisms by Chronic-9-Tetrahydrocannabinol Administration in Male Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Systems Biology Analysis." This report provides mechanistic insights into their previous observation that THC administration attenuates disease progression in SIV infected macaques (AIDS Research and Human Retroviruses 2011; 27: 585-592).
"To better treat HIV infection, we need a better understanding of how it causes the disease we call AIDS. We also need alternative approaches to treatment," says Thomas Hope, PhD, Editor-in-Chief of AIDS Research and Human Retroviruses and Professor of Cell and Molecular Biology at the Feinberg School of Medicine, Northwestern University, Chicago, IL. "This study is important because it begins to explain how THC can influence disease progression in SIV-infected macaques. It also reveals a new way to slow disease progression."
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