The Dual Effects of Δ<sup>9</sup>-Tetrahydrocannabinol on Cholangiocarcinoma Cells: Anti-Invasion Activity at Low Concentration and Apoptosis Induction at High Concentration

Leelawat, Surang; Leelawat, Kawin; Narong, Siriluck; Matangkasombut, Oraphan

doi:10.1080/07357900903405934

Cited by 16 publications

(10 citation statements)

References 22 publications

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“…Particularly as cannabinoids can have dramatic opposing effects and complex interactions with each other11121415161718192021, investigations that only use one source of material may hinder our understanding of pharmacological and therapeutic effects of Cannabis. Given that the effects of Cannabis may vary depending upon the dose3940, where both the chemotype and the dose are important in the medical effects4142, and the potential harmful effects12, it is crucial for scientific and medical investigations to access the varieties used by patients and recreational users.…”

Section: Discussionmentioning

confidence: 99%

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Vergara

Bidwell

Gaudino

et al. 2017

Sci Rep

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As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S. dispensaries. Most dramatically, NIDA’s varieties contain only 27% of the THC levels and as much as 11–23 times the Cannabinol (CBN) content compared to what is available in the state-legal markets. Research restricted to using the current range of federally-produced Cannabis thus may yield limited insights into the chemical, biological and pharmacological properties, and medical potential of material that is available in the state markets. Investigation is urgently needed on the full diversity of Cannabis chemotypes known to be available to the public.

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Section: Discussionmentioning

confidence: 99%

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Vergara

Bidwell

Gaudino

et al. 2017

Sci Rep

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“…In a Wistar rat model, co-treatment of irinotecan with THC led to decreased hepatic toxicity, which suggested a protective role of THC on liver injury during acute treatment [85]. In cholangiocarcinoma cells (including a patient sample) THC exposure suppressed proliferation, migration and invasion, and induced apoptosis [84].…”

Section: Hepatocellular Carcinomamentioning

confidence: 98%

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

162

139

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In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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“…IRE1α promotes Beclin1 liberation from Bcl2 and PI3K-Beclin1 complex activation [163]. This is the case for some drugs such as tetrahydrocannabinol (THC), which exerts its antitumoral action by inducing ER-stress-mediated apoptotic cell death [149,165,166] and has shown anticancer efficacy in CCA [167]. ABTL0812 is the autophagy inductor currently being evaluated in CCA models with the most complete description of its mechanism of action, and it already showed preliminary clinical efficacy on a CCA patient derived from a phase I trial in patients with solid tumors [160,168].…”

Section: Autophagy Activatorsmentioning

confidence: 99%

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Pérez‐Montoyo

2020

Cells

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Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumor microenvironment, but also to increase invasiveness and resistance to anticancer drugs such as chemotherapy. This review collects clinical evidence of autophagy deregulation during cholangiocarcinogenesis together with preclinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggest an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Preclinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer.

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The Dual Effects of Δ⁹-Tetrahydrocannabinol on Cholangiocarcinoma Cells: Anti-Invasion Activity at Low Concentration and Apoptosis Induction at High Concentration

Cited by 16 publications

References 22 publications

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

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The Dual Effects of Δ9-Tetrahydrocannabinol on Cholangiocarcinoma Cells: Anti-Invasion Activity at Low Concentration and Apoptosis Induction at High Concentration

Cited by 16 publications

References 22 publications

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

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Product

Resources

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The Dual Effects of Δ⁹-Tetrahydrocannabinol on Cholangiocarcinoma Cells: Anti-Invasion Activity at Low Concentration and Apoptosis Induction at High Concentration