An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma

Our plain-English summary of An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma, by E.K. Colvin, A.L. Hudson, L.L. Anderson, et al (Cancers, 2022).

The study

• Authors: E.K. Colvin, A.L. Hudson, L.L. Anderson, R.P. Kumar, I.S. McGregor, V.M. Howell, J.C. Arnold
• Journal: Cancers
• Published: 2022;14(15)
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines. A panel of 13 phytocannabinoids inhibited growth of human (MSTO and H2452) and rat (II-45) mesothelioma cells in vitro, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent compounds. Treatment with CBD or CBG resulted in G0/G1 arrest, delayed entry into S phase and induced apoptosis. CBD and CBG also significantly reduced mesothelioma cell migration and invasion. These effects were supported by changes in the expression of genes associated with the cell cycle, proliferation, and cell movement following CBD or CBG treatment. Gene expression levels of CNR1, GPR55, and 5HT1A also increased with CBD or CBG treatment. However, treatment with CBD or CBG in a syngeneic orthotopic rat mesothelioma model was unable to increase survival. Our data show that cannabinoids have anti-cancer effects on mesothelioma cells in vitro and alternatives of drug delivery may be needed to enhance their effects in vivo.

In plain English

This laboratory and animal study tested whether cannabinoids from the cannabis plant act against mesothelioma. It did not study asbestos exposure. The authors tested 13 phytocannabinoids on two human cell lines derived from pleural mesothelioma patients (MSTO and H2452) and one rat line (II-45). All 13 reduced the viability of all three cell lines, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent. In the cells, CBD and CBG halted the cell cycle at an early stage, induced apoptosis (programmed cell death) and reduced cell migration. They also reduced invasion in the two lines where it could be tested (rat II-45 and human H2452); MSTO cells did not invade. They also changed the expression of many genes, including large increases in some cannabinoid-related receptor genes. Rats were pleurally engrafted with mesothelioma cells. Daily injections of CBD (40 mg/kg) or CBG (100 mg/kg) for 4 weeks did not prolong their survival: median 22 and 25 days, against 23 days for vehicle-only controls. Cisplatin plus pemetrexed chemotherapy did prolong survival (median 28 days). The authors concluded that the cannabinoids had anti-cancer effects on mesothelioma cells in the laboratory. They suggested the rats may not have reached high enough blood levels, so other drug delivery methods may be needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Preclinical laboratory study: experiments on mesothelioma cell lines (in vitro) and a survival experiment in rats (in vivo)
• Who was studied: Two human mesothelioma cell lines derived from pleural mesothelioma patients (MSTO-211H and NCI-H2452) and one rat mesothelioma cell line (II-45). The animal experiments used female Fischer 344 rats. The number of rats in the survival study is not stated in the text.
• Exposure: Treatment with 13 phytocannabinoids in cell culture. In rats, daily intraperitoneal injections of 40 mg/kg CBD or 100 mg/kg CBG for 4 weeks, compared with vehicle-only controls and with cisplatin plus pemetrexed chemotherapy. Asbestos exposure was not studied.
• Main results:
  • All 13 phytocannabinoids reduced the viability of the rat II-45 and human MSTO and H2452 mesothelioma cell lines.
  • CBD and CBG were the most potent at reducing viability of the mesothelioma cell lines.
  • In general, the neutral cannabinoids were more potent than their acid forms.
  • After 24 hours of CBD or CBG treatment, the cell lines showed G0/G1 cell cycle arrest, delayed entry into S phase, and apoptosis.
  • At sub-cytotoxic concentrations, CBD and CBG significantly reduced migration and invasion of the rat II-45 and human H2452 cell lines.
  • MSTO cells could not invade through an extracellular matrix, so invasion was not tested in that line.
  • In all three cell lines, CBD and CBG increased mRNA for the CB1 receptor (CNR1), GPR55 and the 5-HT1a receptor (HTR1A), by as much as approximately 50-fold compared with vehicle-treated cells.
  • CBD treatment changed the expression of 181 genes in MSTO cells and 255 genes in H2452 cells (fold change above 2).
  • Neither CBD nor CBG induced autophagy in the cell lines.
  • In the rat model, cisplatin plus pemetrexed significantly prolonged survival compared with vehicle-treated rats (median 28 days vs 23 days; p less than 0.05). Neither CBD nor CBG prolonged survival.
  • Median survival of CBD-treated rats was 22 days.
  • Median survival of CBG-treated rats was 25 days.
  • Severity of pleural dissemination at endpoint showed no statistical differences between the rat groups.
• The authors' conclusion: The authors concluded that plant cannabinoids had anti-proliferative effects on mesothelioma cells, with CBD and CBG the most potent. They could not show an anti-tumour effect in rats, possibly because blood (plasma) concentrations were too low, so alternative drug delivery methods may be needed.
• Limitations the authors state:
  • The authors stated that the plasma concentrations likely reached in the rats stayed about 3-fold lower than the concentrations needed to reduce cell growth in the laboratory.
  • The authors suggested the lack of survival benefit in rats may also reflect the aggressive, rapid growth of the II45 cell line in the animals.
  • Mesothelioma cells have high basal levels of autophagy, so the authors noted that induction of autophagy may be difficult to identify.
  • Invasion could not be tested in the MSTO cell line because those cells did not invade.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis, Palliative Care, Apoptosis.

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