Characterization of cannabinoid receptors expressed in Ewing sarcoma TC-71 and A-673 cells as potential targets for anti-cancer drug development

Shoeib, Amal; Yarbrough, Azure; Ford, Benjamin M.; Franks, Lirit N.; Urbaniak, Alicja; Hensley, Lori L.; Benson, Lance N.; Mu, Shengyu; Radominska‐Pandya, Anna; Prather, Paul L.

doi:10.1016/j.lfs.2021.119993

Cited by 2 publications

(11 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current study confirms and expands on our recently reported findings in Ewing sarcoma (a form of pediatric bone cancer) [33], namely, that several additional cancer types, derived from mouse (C6-glioma), rat (PC-12) and human (HeLa, PC-3, DU-145) origins, similarly express CBRs exhibiting atypical receptor binding and signaling properties rela-tive to canonical CB1 and/or CB2 receptors. Importantly, cannabinoid ligands exhibiting high affinity for these non-canonical CBRs induce cytotoxicity and mitochondrial injury in prostate cancer cells.…”

Section: Discussionsupporting

confidence: 91%

“…Taken together, the results from these binding screens strongly indicate that CBRs expressed in a variety of cancer cell types exhibit atypical binding properties relative to canonical CBRs, with specific binding being detected using [ 3 H]WIN-55-212-2 but not [ 3 H]CP-55,940. The presence of potential "non-canonical" CBRs in cancer cell lines suggested by these results is similar to observations reported previously by our group for CBRs expressed in Ewing sarcoma cell lines [33].…”

Section: Competitive Receptor Binding: Cbrs Expressed In a Variety Of...supporting

confidence: 91%

“…As observed with results obtained using [ 3 H]CP-55,940 (and as expected), in cells/tissues expressing canonical CB1 and CB2 receptors, both CP-55,940 and WIN-55,212-2 (1 µM) produced near or complete displacement of [ 3 H]CP-55,940 (Figure 1B; left 3 panels). As indicated in Figure 1A, the binding data presented for CHO-hCB1 and CHO-hCB2 cells have been previously reported by us [33]. However, and strikingly distinct, when examining binding in various cancer cells (C6-glioma, PC-12, HeLa, PC-3, and DU-145), only WIN-55,212-2, and not CP-55,940, significantly displaced [ 3 H]CP-55,940 (Figure 1B; right 5 panels).…”

Section: Competitive Receptor Binding: Cbrs Expressed In a Variety Of...supporting

confidence: 82%

“…As expected, in CHO cells stably expressing either canonical human CB1 or CB2 receptors (CHO-hCB1 and CHO-hCB2, respectively) or in membranes prepared from mouse brain containing a high density of mouse CB1 receptors (mCB1), both CP-55,940, and WIN-55,212-2 (1 μM) produced near or complete displacement of [ 3 H]CP-55,940 ( Figure 1 A; left 3 panels). The binding data presented for CHO-hCB1 and CHO-hCB2 cells have been previously reported by our laboratory [ 33 ]. In marked contrast (and unexpectedly), when using membranes prepared from all cancer cell lines examined (C6-glioma, PC-12, HeLa, PC-3, and DU-145), neither the non-selective CBR ligand CP-55,940 nor WIN-55,212-2 produced significant displacement of [ 3 H]CP-55,940 ( Figure 1 A; right 5 panels).…”

Section: Resultsmentioning

confidence: 99%

“…Our laboratory recently reported that TC-71 and A-673 Ewing sarcoma (EWS) cell lines (a form of pediatric bone cancer) express high levels of non-canonical CBRs that exhibit distinct binding and signaling profiles, and ligands binding with high affinity to these receptors produce cytotoxicity and cell death [ 33 ]. In the present study, it was hypothesized that other cancer types similarly express non-canonical CBRs and that drugs targeting these receptors will impact tumor cell growth and proliferation.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Non-Canonical Cannabinoid Receptors with Distinct Binding and Signaling Properties in Prostate and Other Cancer Cell Types Mediate Cell Death

Shoeib

Benson

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Cannabinoids exert anti-cancer actions; however, the underlying cytotoxic mechanisms and the cannabinoid receptors (CBRs) involved remain unclear. In this study, CBRs were characterized in several cancer cell lines. Radioligand binding screens surprisingly revealed specific binding only for the non-selective cannabinoid [3H]WIN-55,212-2, and not [3H]CP-55,940, indicating that the expressed CBRs exhibit atypical binding properties. Furthermore, [3H]WIN-55,212-2 bound to a single site in all cancer cells with high affinity and varying densities. CBR characteristics were next compared between human prostate cancer cell lines expressing low (PC-3) and high (DU-145) CBR density. Although mRNA for canonical CBRs was detected in both cell lines, only 5 out of 15 compounds with known high affinity for canonical CBRs displaced [3H]WIN-55,212-2 binding. Functional assays further established that CBRs in prostate cancer cells exhibit distinct signaling properties relative to canonical Gi/Go-coupled CBRs. Prostate cancer cells chronically exposed to both CBR agonists and antagonists/inverse agonists produced receptor downregulation, inconsistent with actions at canonical CBRs. Treatment of DU-145 cells with CBR ligands increased LDH-release, decreased ATP-dependent cell viability, and produced mitochondrial membrane potential depolarization. In summary, several cancer cell lines express CBRs with binding and signaling profiles dissimilar to canonical CBRs. Drugs selectively targeting these atypical CBRs might exhibit improved anti-cancer properties.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Competitive Receptor Binding: Cbrs Expressed In a Variety Of...supporting

confidence: 91%

Section: Competitive Receptor Binding: Cbrs Expressed In a Variety Of...supporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Non-Canonical Cannabinoid Receptors with Distinct Binding and Signaling Properties in Prostate and Other Cancer Cell Types Mediate Cell Death

Shoeib

Benson

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Opposing Effects of Cannabidiol in Patient-derived Neuroendocrine Tumor, Pheochromocytoma/Paraganglioma Primary Cultures

Wang,

Schober,

Fischer

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Context Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (together PPGLs) are still limited. In recent years, anti-tumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs. Objective Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines. Methods We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at two centers. Treatment of patient primary cultures with clinically relevant doses (5 µM) and slightly higher doses (10 µM) of CBD was performed. Results We found opposing effects of 5 µM CBD: significant anti-tumor effects in 5/35 (14%) and significant tumor-promoting effects in 6/35 (17%) of PPGL primary cultures. In terms of anti-tumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (p = 0.042). Of the cluster 2-related tumors, NF1 PPGLs showed strongest responsivity (4/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10 µM CBD in PPGLs and NETs: significant anti-tumor effects in 9/33 of PPGL (27%) and 3/11 of NET (27%) primary cultures, significant tumor-promoting effects in 6/33 of PPGL (18%) and 2/11 of NET (18%) primary cultures. Conclusions We suggest a potential novel treatment option for some NETs/PPGLs, but also provide evidence for caution when applying cannabinoids as supportive therapy for pain or appetite management to cancer patients, and possibly as health supplements.

show abstract

Characterization of cannabinoid receptors expressed in Ewing sarcoma TC-71 and A-673 cells as potential targets for anti-cancer drug development

Cited by 2 publications

References 62 publications

Non-Canonical Cannabinoid Receptors with Distinct Binding and Signaling Properties in Prostate and Other Cancer Cell Types Mediate Cell Death

Non-Canonical Cannabinoid Receptors with Distinct Binding and Signaling Properties in Prostate and Other Cancer Cell Types Mediate Cell Death

Opposing Effects of Cannabidiol in Patient-derived Neuroendocrine Tumor, Pheochromocytoma/Paraganglioma Primary Cultures

Contact Info

Product

Resources

About