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大麻素衍生化合物大麻色烯和 Δ9-四氢大麻酚相互作用并表现出细胞毒性活性，可抑制细胞迁移和细胞骨架组织，与尿路上皮细胞癌相关。

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization.

机构信息

Department of Urology, Sheba Medical Center, 52621 Ramat Gan, Israel.

Institute of Plant Science, Agriculture Research Organization, Volcani Center, 7505101 Rishon LeZion, Israel.

出版信息

Molecules. 2021 Jan 17;26(2):465. doi: 10.3390/molecules26020465.

DOI:10.3390/molecules26020465
PMID:33477303
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7830447/
Abstract

contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.

摘要

大麻含有超过 500 种成分，但绝大多数大麻化合物的抗癌特性仍不清楚。我们旨在确定大麻化合物及其组合对膀胱尿路上皮癌（UC）的细胞毒性，UC 是最常见的泌尿系统癌症。使用 XTT 测定法来确定提取物对 T24 和 HBT-9 细胞系的细胞毒性活性。通过高效液相色谱法（HPLC）鉴定提取物的化学成分。使用染色的 F-肌动蛋白和细胞核，荧光激活细胞分选（FACS）用于确定细胞凋亡和细胞周期。划痕和 Transwell 测定分别用于确定细胞迁移和侵袭。通过定量聚合酶链反应（PCR）确定基因表达。发现高大麻二酚（CBD）脱羧提取物（F7）最具活性，其含有大麻色烯（CBC）和Δ9-四氢大麻酚（THC）。CBC+THC 之间表现出协同相互作用，而大麻素受体（CB）1 型和 2 型反向激动剂降低了细胞毒性活性。CBC+THC 或 CBD 的处理导致细胞周期停滞和细胞凋亡。CBC+THC 或 CBD 处理抑制细胞迁移并影响 F-肌动蛋白完整性。鉴定出大麻中具有诱导细胞凋亡和影响 UC 细胞系细胞迁移的活性植物成分（API），为 UC 治疗的临床前试验奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/6abe1649abbc/molecules-26-00465-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/e3ead281a357/molecules-26-00465-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/f147fa439f29/molecules-26-00465-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/ad710bec3d2a/molecules-26-00465-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/087577da2b92/molecules-26-00465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/9be913445737/molecules-26-00465-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/6abe1649abbc/molecules-26-00465-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/e3ead281a357/molecules-26-00465-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/f147fa439f29/molecules-26-00465-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/ad710bec3d2a/molecules-26-00465-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/087577da2b92/molecules-26-00465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/9be913445737/molecules-26-00465-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f83/7830447/6abe1649abbc/molecules-26-00465-g006.jpg

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