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Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo
Year:
2020
Source of publication :
Oncotarget
Authors :
Doron-Faigenboim, Adi
;
.
Koltai, Hinanit
;
.
Mazuz, Moran
;
.
Nadarajan, Stalin
;
.
Namdar, Dvory
;
.
Vinayaka, Ajjampura C.
;
.
Volume :
11
Co-Authors:

Amir Tiroler - Agricultural Research Organization (ARO), Volcani Center, Rishon LeZion, Israel ; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Lilach Moyal - Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Emmilia Hodak - Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Batia Gorovitz-Haris - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel..
Ido Lubin - Core Facility, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Avi Drori - MedC Biopharma Corporation, Ontario, Canada. 
Guy Drori - MedC Biopharma Corporation, Ontario, Canada. 
Owen Van Cauwenberghe - AgMedica Bioscience Inc., Chatham-Kent, Canada. 
Iris Amitay-Laish - Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Facilitators :
From page:
1141
To page:
1156
(
Total pages:
16
)
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.

Note:
Related Files :
Cannabinoids
Cannabis
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More details
DOI :
10.18632/oncotarget.27528
Article number:
0
Affiliations:
Database:
Google Scholar
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
47360
Last updated date:
09/03/2022 17:08
Creation date:
20/04/2020 21:18
Scientific Publication
Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo
11

Amir Tiroler - Agricultural Research Organization (ARO), Volcani Center, Rishon LeZion, Israel ; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Lilach Moyal - Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Emmilia Hodak - Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Batia Gorovitz-Haris - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel..
Ido Lubin - Core Facility, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Avi Drori - MedC Biopharma Corporation, Ontario, Canada. 
Guy Drori - MedC Biopharma Corporation, Ontario, Canada. 
Owen Van Cauwenberghe - AgMedica Bioscience Inc., Chatham-Kent, Canada. 
Iris Amitay-Laish - Division of Dermatology, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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

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.

Scientific Publication
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