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>
Bibliographic record
Abstract
// Moran Mazuz 1 , * , Amir Tiroler 1 , 2 , * , Lilach Moyal 3 , 4 , Emmilia Hodak 3 , 4 , Stalin Nadarajan 1 , Ajjampura C. Vinayaka 1 , Batia Gorovitz-Haris 4 , Ido Lubin 5 , Avi Drori 6 , Guy Drori 6 , Owen Van Cauwenberghe 7 , Adi Faigenboim 1 , Dvora Namdar 1 , Iris Amitay-Laish 3 , 4 , # and Hinanit Koltai 1 , # 1 Agricultural Research Organization (ARO), Volcani Center, Rishon LeZion, Israel 2 The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel 3 Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 4 Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 5 Core Facility, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 6 MedC Biopharma Corporation, Ontario, Canada 7 AgMedica Bioscience Inc., Chatham-Kent, Canada * These authors equally contributed as the first author # These authors equally contributed as the last author Correspondence to: Hinanit Koltai, email: hkoltai@agri.gov.il Keywords: cutaneous T-cell lymphoma; cannabis; cannabinoids; peripheral blood lymphocytes; CTCL cell lines Received: July 15, 2019     Accepted: March 03, 2020     Published: March 31, 2020 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".