Erzurumlu Yalcin, Catakli Deniz
Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Türkiye.
Department of Drug Research and Development, Institute of Health Sciences, Suleyman Demirel University, Isparta, Türkiye.
Cannabis Cannabinoid Res. 2025 Apr;10(2):258-276. doi: 10.1089/can.2023.0284. Epub 2024 Aug 20.
extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells. Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence. Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities. The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.
自古以来，该提取物就被用作草药。它是研究最多的提取物之一，尤其是在癌症支持治疗方面。前列腺癌是全球男性中最常被诊断出的癌症类型之一，2023年估计有288,300例新病例被诊断出来。如今，许多先进的治疗方法被用于前列腺癌，如免疫疗法和化疗，但获得性耐药、长期用药以及癌细胞分化大多限制了治疗效果。因此，人们认为使用天然产物来克服这些限制并提高现有疗法的有效性可能提供有前景的方法。本研究重点调查了大麻二酚（CBD），一种大麻的有效成分化合物，对前列腺癌细胞中化疗药物依托泊苷可能的增强作用。在此，我们通过测试细胞毒性作用、形态改变、凋亡效应、自噬、未折叠蛋白反应（UPR）信号传导、内质网相关降解机制（ERAD）、血管生成和雄激素相关因子以及上皮-间质转化（EMT），来检测CBD对前列腺癌细胞中依托泊苷的增强作用。此外，我们研究了CBD与依托泊苷联合治疗对集落生长、迁移、侵袭能力、三维肿瘤形成和细胞衰老的影响。我们的研究结果表明，依托泊苷与CBD联合处理显著抑制了LNCaP细胞中的自噬流，并诱导了ERAD和UPR信号传导。此外，CBD强烈增强了依托泊苷介导的对雄激素信号传导、血管生成因子VEGF-A、原癌基因c-Myc、EMT的抑制作用，还通过激活半胱天冬酶-3和PARP-1诱导凋亡。而且，联合给药显著降低了肿瘤发生特性，如增殖能力、集落生长、迁移和三维肿瘤形成，还诱导了衰老。总之，我们的数据表明CBD对依托泊苷相关的抗癌活性具有强大增强作用。本研究表明，在现有的化疗方法中使用CBD作为支持疗法可能是一个有前景的选择，但这种有效性需要大规模研究。
