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Oncotarget Synergistic cytotoxic activity of cannabinoids from cannabis sativa


FOR IMMEDIATE RELEASE
2020-03-31

The cover for issue 13 of Oncotarget features Figure 5, "Hierarchical clustering and Venn diagram of genes significantly differentially expressed genes in My-La and HuT-78 cells treated with S4, S5 or the S4+S5 synergistic combination," by Mazuz, et al.

This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells.

Active cannabis compounds presenting high cytotoxic activity on My-La and Hu T-78 cell lines were identified in crude extract fractions designated S4 and S5, and their synergistic mixture was specified.

This mixture induced cell cycle arrest and cell apoptosis; a relatively selective apoptosis was also recorded on the malignant CD4+CD26- SPBL cells.

Dr. Hinanit Koltai from the Agricultural Research Organization (ARO), Volcani Center, Rishon LeZion, Israel said "Cannabis sativa has been used by humanity for thousands of years. Initial interest in the plant was likely related to its psychotropic effects."

"Cannabis sativa has been used by humanity for thousands of years. Initial interest in the plant was likely related to its psychotropic effects."

- Dr. Hinanit Koltai, Agricultural Research Organization (ARO), Volcani Center

Sezary syndrome is a rare type of CTCL in which malignant cells circulate in peripheral blood, also referred to as the leukemic phase of erythrodermic CTCLs. On T-cell leukemia cell lines, combinations of THC and CBD, as well as CBD and cannabigerolic acid, were found to elicit cell death when each phytocannabinoid was used alone or in combination with each other.

In addition, despite accumulating knowledge regarding the anti-cancer activity of phytocannabinoids, CB agonists and antagonists, little is known of anti-cancer activity resulting from mixtures of compounds from whole cannabis plant extracts.

In this paper the authors identify active compounds derived from C. sativa whole plant extracts and their synergistic mixtures, which show cytotoxic activity on CTCL cell lines.

Figure 5: Hierarchical clustering and Venn diagram of genes significantly differentially expressed genes in My-La and HuT-78 cells treated with S4, S5 or the S4+S5 synergistic combination. (A) Hierarchical clustering using Pearson correlations among the four conditions based on the genes expression (average fragments per kilobase of transcript per million fragments mapped [FPKM] of the three replications) followed by a log2 transform. Pearson correlations were calculated with the R software package. (B) Venn diagrams illustrating the relationships between significantly differentially expressed genes (padj < 0.05) in the three treatments against the control. Venn diagrams were generated using the online tool at bioinformatics.psb.ugent.be/webtools/Venn/.

This combination of compounds was also active on malignant enriched cells of peripheral blood lymphocytes from Sezary patients.

The Koltai Research Team concluded in their Oncotarget Research Paper, "active cannabis extract fractions and their synergistic combinations were cytotoxic to CTCL cell lines in in-vitro and to SPBL in ex-vivo studies. The defined S4+S5 formulation of synergistic phytocannabinoids induced cell cycle arrest and cell apoptosis, and affected multiple biological pathways, including those associated with cancer. Based on this preclinical study new cannabis-based products that are based on precise composition of synergistically interacting compounds may be developed. Human clinical trials are needed to validate the effectiveness of these synergistic cannabis compounds of active pharmaceutical ingredients for the treatment of CTCL."

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DOI - https://doi.org/10.18632/oncotarget.27528

Full text - https://www.oncotarget.com/article/27528/text/

Correspondence to - Hinanit Koltai - hkoltai@agri.gov.il

Keywords - cutaneous+T-cell+lymphoma, cannabis, cannabinoids, peripheral blood lymphocytes, CTCL cell lines

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