关键词: apoptose apoptosis breast cancer cancer du sein cannabis chemotherapeutic resistance résistance à la chimiothérapie synergie synergy terpenes terpènes

Mesh : Antineoplastic Agents Breast Neoplasms / drug therapy Cannabinoid Receptor Agonists Cannabinoids / pharmacology therapeutic use Cannabis Female Flavonoids Humans Paclitaxel / pharmacology therapeutic use Terpenes / pharmacology therapeutic use

来  源:   DOI:10.1139/cjpp-2021-0792

Abstract:
Chemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aimed to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and whether their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and β-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade, and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and β-myrcene. Combinations of nerolidol and Δ9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer.
摘要:
化疗耐药可能会限制乳腺癌的预后;因此,有必要探索新的治疗方案.在大麻中发现的分离化合物先前已被证明具有抗癌作用,但对它们在耐药乳腺癌中的作用知之甚少。我们的研究旨在评估大麻中发现的萜烯在乳腺癌体外化疗耐药模型中的作用。我们的目的是确定大麻中发现的五种萜烯是否具有抗癌作用,以及与大麻中也发现的大麻素和类黄酮共同治疗后,它们的效果是否得到改善。橙花醇和β-石竹烯产生最大的细胞毒性作用,激活了凋亡级联,减少细胞入侵。与黄酮类山奈酚的组合增强了新烯的细胞毒性作用,terpinolene,和β-月桂烯。nerolidol和Δ9-四氢大麻酚或大麻二酚的组合产生了从拮抗作用和加和作用到协同作用的可变反应,取决于使用的浓度。我们的结果表明,大麻萜烯,单独或与大麻素和类黄酮组合,在化疗耐药的乳腺癌细胞系中产生抗癌作用。这项研究是鉴定化合物的第一步,这些化合物可能具有治疗耐药性乳腺癌的治疗潜力。
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