Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 8/2023

27-02-2023 | osteosarcoma | RESEARCH ARTICLE

The synergistic anticancer effect of CBD and DOX in osteosarcoma

Authors: Juncheng Li, Wei Jiang, Wenhao Shan, Aiying Luo, Gaoyang Qu, Jiongfeng Zhang, Xiaohui Luo, Jian Xia

Published in: Clinical and Translational Oncology | Issue 8/2023

Login to get access

Abstract

Background

Osteosarcoma is a malignant tumor that can present with pain in the bones, joints, and local masses. The incidence is highest in adolescents, and the most common sites are the distal femur, proximal tibia and proximal humerus metaphyseal. Doxorubicin is the first-line chemotherapeutic agent for the treatment of osteosarcoma, but it has many side effects. Cannabidiol is a non-psychoactive plant cannabinoid cannabinol (CBD) that has been shown to be effective against osteosarcoma; however, the molecular targets and mechanisms of CBD action in osteosarcoma remain unclear.

Methods

Cell proliferation, migration, invasion and colony formation were analyzed using two drugs alone or in combination to evaluate their inhibitory effects on the malignant characteristics of OS cells. Apoptosis and the cell cycle were detected by flow cytometry. The synergistic inhibitory effect of doxorubicin/cannabidiol on tumors was also detected in nude mouse xenotransplantation models.

Results

Through analysis of two osteosarcoma cell lines, MG63 and U2R, it was found that the cannabidiol/doxorubicin combination treatment synergistically inhibited growth, migration and invasion and induced apoptosis, blocking G2 stagnation in OS cells. Further mechanistic exploration suggests that the PI3K-AKT-mTOR pathway and MAPK pathway play an important role in the synergistic inhibitory effect of the two drugs in osteosarcoma. Finally, in vivo experimental results showed that the cannabidiol/doxorubicin combination treatment significantly reduced the number of tumor xenografts compared to cannabidiol alone or doxorubicin alone.

Conclusions

Our findings in this study suggest that cannabidiol and doxorubicin have a synergistic anticancer effect on OS cells, and their combined application may be a promising treatment strategy for OS.
Literature
1.
Lamoureux F, Trichet V, Chipoy C, Blanchard F, Gouin F, Redini F. Recent advances in the management of osteosarcoma and forthcoming therapeutic strategies. Expert Rev Anticancer Ther. 2007;7(2):169–81.CrossRefPubMed
2.
Raymond AK, Jaffe N. Osteosarcoma multidisciplinary approach to the management from the pathologist’s perspective. Cancer Treat Res. 2009;152:63–84.CrossRefPubMed
3.
Alessandra L, Costantino E, Paolis MD, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev. 2006;32(6):423–36.CrossRef
4.
Cao C, Wang Q, Liu Y. Lung cancer combination therapy: doxorubicin and beta-elemene co-loaded, pH-sensitive nanostructured lipid carriers. Drug Des Devel Ther. 2019;13:1087–98.CrossRefPubMedPubMedCentral
5.
Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther. 2011;10(7):1161–72.CrossRefPubMed
6.
Vaccani A, Massi P, Colombo A, Rubino T, Parolaro D. Cannabidiol inhibits human glioma cell migration through a cannabinoid. Br J Pharmacol. 2005;144(8):1032–6.CrossRefPubMedPubMedCentral
7.
Solinas M, Massi P, Cinquina V, Valenti M, Bolognini D, Gariboldi M, et al. Cannabidiol, a non-psychoactive cannabinoid compound, inhibits proliferation and invasion in U87-MG and T98G glioma cells through a multitarget effect. PLoS ONE. 2013;8(10): e76918.CrossRefPubMedPubMedCentral
8.
Milian L, Mata M, Alcacer J, Oliver M, Sancho-Tello M, Martin de Llano JJ, et al. Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. PLoS ONE. 2020;15(2):0228909.CrossRef
9.
Xu F, Sun G, Peng Z, Liu J, Li Z, Yan J. Cannabidiol promotes apoptosis of osteosarcoma cells in vitro and in vivo by activating the SP1-CBX2 axis. Am J Translat Res. 2022;14(2):1188–203.
10.
Zuardi WA. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Br Psiquiatria. 2008;30(3):271–80.CrossRef
11.
Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39(2):167–79.CrossRefPubMed
12.
Philpott HT, O’Brien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017;158(12):2442–51.CrossRefPubMedPubMedCentral
13.
Sokolov AM, Holmberg JC, Feliciano DM. The amino acid transporter Slc7a5 regulates the mTOR pathway and is required for granule cell development. Hum Mol Genet. 2020;29(18):3003–13.CrossRefPubMedPubMedCentral
14.
Joassard OR, Amirouche A, Gallot YS, Desgeorges MM, Castells J, Durieux AC, et al. Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in response to formoterol administration in rat skeletal muscle. Int J Biochem Cell Biol. 2013;45(11):2444–55.CrossRefPubMed
15.
Li J, Xu Z. NR3C2 suppresses the proliferation, migration, invasion and angiogenesis of colon cancer cells by inhibiting the AKT/ERK signaling pathway. Mol Med Rep. 2022;25:4.CrossRef
16.
Behzad M, Ali M, Sadaf D, Solmaz S, Behzad B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharmaceut Bull. 2017;7(3):339–48.CrossRef
17.
Bielack SS, Smeland S, Whelan JS, Marina N, Jovic G, Hook JM, et al. Methotrexate, doxorubicin, and cisplatin (MAP) plus maintenance pegylated interferon Alfa-2b versus MAP alone in patients with resectable high-grade osteosarcoma and good histologic response to preoperative map: first results of the EURAMOS-1 good response randomized controlled trial. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(20):2279–87.CrossRef
18.
Patra PH, Barker-Haliski M, White HS, Whalley BJ, Glyn S, Sandhu H, et al. Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models. Epilepsia. 2019;60(2):303–14.CrossRefPubMed
19.
Lowin T, Tingting R, Zurmahr J, Classen T, Schneider M, Pongratz G. Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis. 2020;11(8):714.CrossRefPubMedPubMedCentral
20.
Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer. 2009;115(7):1531–43.CrossRefPubMed
21.
Yang C, Tian Y, Zhao F, Chen Z, Su P, Li Y, et al. Bone microenvironment and osteosarcoma metastasis. Int J Mol Sci. 2020;21:19.
Metadata
Title
The synergistic anticancer effect of CBD and DOX in osteosarcoma
Authors
Juncheng Li
Wei Jiang
Wenhao Shan
Aiying Luo
Gaoyang Qu
Jiongfeng Zhang
Xiaohui Luo
Jian Xia
Publication date
27-02-2023
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 8/2023
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-023-03119-3

Other articles of this Issue 8/2023

Clinical and Translational Oncology 8/2023 Go to the issue

RESEARCH ARTICLE

Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma

REVIEW ARTICLE

Lung microbiome: an emerging player in lung cancer pathogenesis and progression

REVIEW ARTICLE

Chimeric antigen receptor T cells therapy in solid tumors

RESEARCH ARTICLE

Clinical characteristics of pediatric allogeneic hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA): a retrospective single-center analysis

RESEARCH ARTICLE

Synergistic effect of chrysin and radiotherapy against triple-negative breast cancer (TNBC) cell lines

REVIEW ARTICLE

Purinergic P2X7R as a potential target for pancreatic cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits