Tomko Andrea M, Whynot Erin G, O'Leary Lauren F, Dupré Denis J
Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
Can J Physiol Pharmacol. 2022 Aug 1;100(8):806-817. doi: 10.1139/cjpp-2021-0792. Epub 2022 Jun 15.
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.
化疗耐药会限制乳腺癌的治疗效果；因此，探索新的治疗方案很有必要。此前已表明，大麻中分离出的化合物具有抗癌作用，但对于它们在耐药乳腺癌中的作用却知之甚少。我们的研究旨在评估大麻中发现的萜类化合物在体外乳腺癌化疗耐药模型中的作用。我们旨在确定大麻中发现的五种萜类化合物是否具有抗癌作用，以及它们与大麻中也含有的大麻素和黄酮类化合物联合使用时效果是否会增强。橙花叔醇和β-石竹烯产生的细胞毒性作用最大，激活了凋亡级联反应，并减少了细胞侵袭。与黄酮类化合物山奈酚联合使用增强了罗勒烯、萜品油烯和β-月桂烯的细胞毒性作用。橙花叔醇与Δ9-四氢大麻酚或大麻二酚联合使用时，根据所用浓度不同，产生的反应从拮抗、相加到协同不等。我们的结果表明，大麻萜类化合物单独使用或与大麻素和黄酮类化合物联合使用时，在化疗耐药的乳腺癌细胞系中具有抗癌作用。这项研究是鉴定可能对耐药乳腺癌具有治疗潜力的化合物的第一步。
