大麻素在前列腺癌和结肠癌细胞中诱导细胞凋亡依赖于磷酸酶。
Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.
机构信息
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
出版信息
Anticancer Res. 2011 Nov;31(11):3799-807.
Abstract
AIM
We hypothesized that the anticancer activity of cannabinoids was linked to induction of phosphatases.
MATERIALS AND METHODS
The effects of cannabidiol (CBD) and the synthetic cannabinoid WIN-55,212 (WIN) on LNCaP (prostate) and SW480 (colon) cancer cell proliferation were determined by cell counting; apoptosis was determined by cleavage of poly(ADP)ribose polymerase (PARP) and caspase-3 (Western blots); and phosphatase mRNAs were determined by real-time PCR. The role of phosphatases and cannabinoid receptors in mediating CBD- and WIN-induced apoptosis was determined by inhibition and receptor knockdown.
RESULTS
CBD and WIN inhibited LNCaP and SW480 cell growth and induced mRNA expression of several phosphatases, and the phosphatase inhibitor sodium orthovanadate significantly inhibited cannabinoid-induced PARP cleavage in both cell lines, whereas only CBD-induced apoptosis was CB1 and CB2 receptor-dependent.
CONCLUSION
Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.
摘要
目的
我们假设大麻素的抗癌活性与磷酸酶的诱导有关。
材料和方法
通过细胞计数来确定大麻二酚 (CBD) 和合成大麻素 WIN-55,212 (WIN) 对 LNCaP（前列腺）和 SW480（结肠）癌细胞增殖的影响；通过多聚（ADP-核糖）聚合酶 (PARP) 和半胱天冬酶-3 (Western blot) 的切割来确定细胞凋亡；通过实时 PCR 确定磷酸酶 mRNA。通过抑制和受体敲低来确定磷酸酶和大麻素受体在介导 CBD 和 WIN 诱导的细胞凋亡中的作用。
结果
CBD 和 WIN 抑制了 LNCaP 和 SW480 细胞的生长，并诱导了几种磷酸酶的 mRNA 表达，而磷酸酶抑制剂正钒酸钠在两种细胞系中均显著抑制了大麻素诱导的 PARP 切割，而只有 CBD 诱导的细胞凋亡依赖于 CB1 和 CB2 受体。
结论
大麻素受体激动剂在癌细胞系中诱导磷酸酶和磷酸酶依赖性细胞凋亡；然而，CB 受体在介导这种反应中的作用是配体依赖性的。
相似文献
1
Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.大麻素在前列腺癌和结肠癌细胞中诱导细胞凋亡依赖于磷酸酶。
Anticancer Res. 2011 Nov;31(11):3799-807.
2
Cannabinoid receptor as a novel target for the treatment of prostate cancer.大麻素受体作为治疗前列腺癌的新靶点。
Cancer Res. 2005 Mar 1;65(5):1635-41. doi: 10.1158/0008-5472.CAN-04-3410.
3
Involvement of the CB cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212-2 in renal cell carcinoma.大麻素 CB 受体通过大麻素激动剂 WIN 55,212-2 参与肾细胞癌细胞生长抑制和 G0/G1 细胞周期阻滞。
BMC Cancer. 2018 May 23;18(1):583. doi: 10.1186/s12885-018-4496-1.
4
The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.大麻素WIN 55,212-2可阻止LNCaP前列腺癌细胞的神经内分泌分化。
Prostate Cancer Prostatic Dis. 2016 Sep;19(3):248-57. doi: 10.1038/pcan.2016.19. Epub 2016 Jun 21.
5
Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer.合成大麻素受体激动剂抑制乳腺癌的生长和转移。
Mol Cancer Ther. 2009 Nov;8(11):3117-29. doi: 10.1158/1535-7163.MCT-09-0448. Epub 2009 Nov 3.
6
Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.大麻素 WIN 55,212-2 可诱导细胞周期停滞和细胞凋亡，并通过大麻素受体 2 依赖性方式抑制前列腺癌的增殖、迁移、侵袭和肿瘤生长。
Prostate. 2019 Feb;79(2):151-159. doi: 10.1002/pros.23720. Epub 2018 Sep 21.
7
The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro.CB1/CB2受体激动剂WIN-55,212-2在体外可降低人卡波西肉瘤细胞的活力。
Eur J Pharmacol. 2009 Aug 15;616(1-3):16-21. doi: 10.1016/j.ejphar.2009.06.004. Epub 2009 Jun 17.
8
Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis.大麻素受体，CB1 和 CB2，作为抑制非小细胞肺癌生长和转移的新靶点。
Cancer Prev Res (Phila). 2011 Jan;4(1):65-75. doi: 10.1158/1940-6207.CAPR-10-0181. Epub 2010 Nov 19.
9
Characterization of cannabinoid receptors expressed in Ewing sarcoma TC-71 and A-673 cells as potential targets for anti-cancer drug development.描述表达于尤因肉瘤 TC-71 和 A-673 细胞中的大麻素受体，作为抗癌药物开发的潜在靶点。
Life Sci. 2021 Nov 15;285:119993. doi: 10.1016/j.lfs.2021.119993. Epub 2021 Sep 28.
10
Inhibition of spontaneous neurotransmission in the nucleus of solitary tract of the rat by the cannabinoid agonist WIN 55212-2 is not via CB1 or CB2 receptors.大麻素激动剂WIN 55212-2对大鼠孤束核中自发性神经传递的抑制作用并非通过CB1或CB2受体介导。
Brain Res. 2008 Mar 20;1200:1-9. doi: 10.1016/j.brainres.2008.01.011. Epub 2008 Jan 16.
引用本文的文献
1
Cannabidiol (CBD) and Colorectal Tumorigenesis: Potential Dual Modulatory Roles via the Serotonergic Pathway.大麻二酚（CBD）与结直肠癌发生：通过5-羟色胺能途径发挥潜在的双重调节作用
Curr Oncol. 2025 Jun 26;32(7):375. doi: 10.3390/curroncol32070375.
2
Targeting Gastrointestinal Cancers with Cannabidiol: Mechanisms, Challenges, and Therapeutic Implications.用大麻二酚靶向治疗胃肠道癌症：作用机制、挑战及治疗意义
Med Oncol. 2025 Jun 3;42(7):237. doi: 10.1007/s12032-025-02790-6.
3
Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies.大麻二酚诱导肿瘤细胞死亡的机制：临床前研究综述
Plants (Basel). 2025 Feb 14;14(4):585. doi: 10.3390/plants14040585.
4
Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS-STING Pathway in Triple-Negative Breast Cancer Cells.大麻二酚通过cGAS-STING途径上调三阴性乳腺癌细胞中PD-L1的表达来增强阿替利珠单抗的疗效。
Cancer Immunol Res. 2024 Dec 3;12(12):1796-1807. doi: 10.1158/2326-6066.CIR-23-0902.
5
A Bioinformatic Analysis Predicts That Cannabidiol Could Function as a Potential Inhibitor of the MAPK Pathway in Colorectal Cancer.一项生物信息学分析预测，大麻二酚可能作为一种潜在的抑制剂作用于结直肠癌中的丝裂原活化蛋白激酶（MAPK）信号通路。
Curr Issues Mol Biol. 2024 Aug 5;46(8):8600-8610. doi: 10.3390/cimb46080506.
6
From bench to bedside: the application of cannabidiol in glioma.从实验室到临床：大麻二酚在神经胶质瘤中的应用。
J Transl Med. 2024 Jul 11;22(1):648. doi: 10.1186/s12967-024-05477-0.
7
Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol.大麻二酚抗肿瘤作用机制的研究进展。
Molecules. 2024 Apr 24;29(9):1943. doi: 10.3390/molecules29091943.
8
Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells.大麻二酚抑制前列腺癌细胞的增殖和侵袭。
J Nat Prod. 2023 Sep 22;86(9):2151-2161. doi: 10.1021/acs.jnatprod.3c00363. Epub 2023 Sep 13.
9
Molecular and Cellular Mechanisms of Action of Cannabidiol.大麻素的分子和细胞作用机制。
Molecules. 2023 Aug 9;28(16):5980. doi: 10.3390/molecules28165980.
10
Antitumor Effects of Bioactive Compounds on Colorectal Carcinogenesis.生物活性化合物对结直肠癌发生的抗肿瘤作用。
Biomolecules. 2023 Apr 28;13(5):764. doi: 10.3390/biom13050764.
本文引用的文献
1
Deletion of the dual specific phosphatase-4 (DUSP-4) gene reveals an essential non-redundant role for MAP kinase phosphatase-2 (MKP-2) in proliferation and cell survival.删除双重特异性磷酸酶-4（DUSP-4）基因揭示了丝裂原活化蛋白激酶磷酸酶-2（MKP-2）在增殖和细胞存活中的必不可少的非冗余作用。
J Biol Chem. 2011 Apr 15;286(15):12933-43. doi: 10.1074/jbc.M110.181370. Epub 2011 Feb 11.
2
Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells.铁皮石斛酚 A 抑制人乳腺癌细胞中转录激活子 3 的激活。
Carcinogenesis. 2010 Nov;31(11):1991-8. doi: 10.1093/carcin/bgq175. Epub 2010 Aug 19.
3
Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth.人前列腺酸性磷酸酶，一种真正的酪氨酸磷酸酶，使 ErbB-2 去磷酸化并调节前列腺癌细胞生长。
J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub 2010 May 24.
4
Effect of a synthetic cannabinoid agonist on the proliferation and invasion of gastric cancer cells.合成大麻素激动剂对胃癌细胞增殖和侵袭的影响。
J Cell Biochem. 2010 May 15;110(2):321-32. doi: 10.1002/jcb.22540.
5
Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression.姜黄素抑制人胰腺癌细胞系中组成性 STAT3 磷酸化和 survivin/BIRC5 基因表达下调。
Cancer Invest. 2010 Feb;28(2):166-71. doi: 10.3109/07357900903287006.
6
Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP-1 in human multiple myeloma cells.桦木酸通过诱导人多发性骨髓瘤细胞中的蛋白酪氨酸磷酸酶 SHP-1 来抑制 STAT3 激活途径。
Int J Cancer. 2010 Jul 15;127(2):282-92. doi: 10.1002/ijc.25059.
7
Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1.大麻二酚通过上调基质金属蛋白酶组织抑制剂-1 抑制癌细胞侵袭。
Biochem Pharmacol. 2010 Apr 1;79(7):955-66. doi: 10.1016/j.bcp.2009.11.007. Epub 2009 Nov 13.
8
1,1-Bis(3'-indolyl)-1-(p-bromophenyl)methane and related compounds repress survivin and decrease gamma-radiation-induced survivin in colon and pancreatic cancer cells.1,1-双（3'-吲哚基）-1-（对溴苯基）甲烷及相关化合物可抑制结肠癌细胞和胰腺癌细胞中的生存素，并降低γ射线诱导的生存素水平。
Int J Oncol. 2009 Nov;35(5):1191-9. doi: 10.3892/ijo_00000436.
9
Inhibition of NF-kappaB-dependent transcription by MKP-1: transcriptional repression by glucocorticoids occurring via p38 MAPK.MKP-1对核因子κB依赖性转录的抑制作用：糖皮质激素通过p38丝裂原活化蛋白激酶实现转录抑制
J Biol Chem. 2009 Sep 25;284(39):26803-15. doi: 10.1074/jbc.M109.028381. Epub 2009 Jul 31.
10
Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation.2型大麻素受体激活可诱导小胶质细胞产生抗炎表型，并通过诱导MKP和ERK去磷酸化减少其迁移。
Mol Pain. 2009 May 28;5:25. doi: 10.1186/1744-8069-5-25.
Zotero 插件