| Autor: |
Swati Misri, Kirti Kaul, Sanjay Mishra, Manish Charan, Ajeet Kumar Verma, Martin P. Barr, Dinesh K. Ahirwar, Ramesh K. Ganju |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancers; Volume 14; Issue 5; Pages: 1181 |
| ISSN: |
2072-6694 |
| Popis: |
Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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