Dataset Information

Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo.

ABSTRACT: Cannabis sativa produces hundreds of phytocannabinoids and terpenes. Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood. This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells. Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Cytotoxic activity was determined using the XTT assay on My-La and HuT-78 cell lines as well as peripheral blood lymphocytes from Sézary patients (SPBL). Annexin V assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle. RNA sequencing and quantitative PCR were used to determine gene expression. Active cannabis compounds presenting high cytotoxic activity on My-La and HuT-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. Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5. The gene expression profile was distinct in My-La and HuT-78 cells treated with the S4 and S5 synergistic mixture. We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies.

SUBMITTER: Mazuz M

PROVIDER: S-EPMC7138167 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo.

Mazuz Moran M Tiroler Amir A Moyal Lilach L Hodak Emmilia E Nadarajan Stalin S Vinayaka Ajjampura C AC Gorovitz-Haris Batia B Lubin Ido I Drori Avi A Drori Guy G Cauwenberghe Owen Van OV Faigenboim Adi A Namdar Dvora D Amitay-Laish Iris I Koltai Hinanit H

Oncotarget 20200331 13

Cannabis sativa produces hundreds of phytocannabinoids and terpenes. Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood. This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL ...[more]

PMID: 32284791

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Project description:Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we study miRNA expression in 199 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Q-RT-PCR analysis of 104 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A q-RT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL. miRNA microarray. From each sample 100 ng of total RNA was labeled with Hy3 fluorescent dye using the miRCURY LNA Array power labeling kit (Exiqon, Denmark). All samples were labeled the same day with the same master mix, in order to minimize technical variation. The Hy3-labelled samples were hybridized to miRCURY LNA arrays (v11.0) (Exiqon, Denmark), containing capture probes targeting all human miRNAs registered in the miRBASE version 15.0 at the Sanger Institute. The hybridization was performed overnight at 56Â°C according to manufacturer specifications using a Tecan HS4800 hybridization station (Tecan, Austria). Since it was not possible to hybridize all arrays in one go, samples were randomly split into 5 batches as to minimize day to day variation in the hybridization process. After hybridization the microarray slides were scanned using an Agilent G2565BA Microarray Scanner System (Agilent Technologies, Inc., USA) at 5Âµm resolution, and the resulting TIFF images were analyzed using the ImaGene 8.0 software on standard settings (BioDiscovery, Inc., USA).

Dataset Information

Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo.

Publications

Synergistic cytotoxic activity of cannabinoids from <i>cannabis sativa</i> against cutaneous T-cell lymphoma (CTCL) <i>in-vitro</i> and <i>ex-vivo</i>.

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