Abstract：
Multiple myeloma (MM) is a blood cancer caused by uncontrolled growth of clonal plasmacells. Bone disease is responsible for the severe complications of MM and is caused by myeloma cells infiltrating the bone marrow and inducing osteoclast activation. To date, no treatment for MM is truly curative since patients relapse and become refractory to all drug classes. Cannabinoids are already used as palliative in cancer patients. Furthermore, their proper anticancer effect was demonstrated in many cancer models in vitro, in vivo, and in clinical trials. Anyway, few information was reported on the effect of cannabinoids on MM and no data has been provided on minor phytocannabinoids such as cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and cannabidivarin (CBDV). Scientific literature also reported cannabinoids beneficial effect against bone disease. Here, we examined the cytotoxic activity of CBG, CBC, CBN, and CBDV in vitro in MM cell lines, their effect in modulating MM cells invasion toward bone cells and the bone resorption. Subsequently, according to the in vitro results, we selected CBN for in vivo study in a MM xenograft mice model. Results showed that the phytocannabinoids inhibited MM cell growth and induced necrotic cell death. Moreover, the phytocannabinoids reduced the invasion of MM cells toward osteoblast cells and bone resorption in vitro. Lastly, CBN reduced in vivo tumor mass. Together, our results suggest that CBG, CBC, CBN, and CBDV can be promising anticancer agents for MM.
摘要：
多发性骨髓瘤（MM）是由克隆性浆细胞的不受控制的生长引起的血癌。骨疾病是MM严重并发症的原因，是骨髓瘤细胞浸润骨髓并诱导破骨细胞活化引起的。迄今为止,由于患者复发并且对于所有药物类别都变得难以治疗,因此没有针对MM的治疗是真正治愈的。大麻素已经在癌症患者中用作姑息治疗。此外，它们的抗癌作用在许多体外癌症模型中得到证实，在体内，在临床试验中。不管怎样,关于大麻素对MM的影响的信息很少，没有提供关于小植物大麻素如大麻酚（CBG）的数据，大麻酚（CBC），大麻酚（CBN），和大麻素（CBDV）。科学文献还报道了大麻素对骨骼疾病的有益作用。这里,我们检测了CBG的细胞毒活性,CBC,CBN,和CBDV在MM细胞系中的体外研究，它们在调节MM细胞对骨细胞的侵袭和骨吸收中的作用。随后，根据体外结果,我们选择CBN在MM异种移植小鼠模型中进行体内研究。结果表明，植物大麻素抑制MM细胞生长并诱导坏死细胞死亡。此外，植物大麻素在体外减少了MM细胞对成骨细胞的侵袭和骨吸收。最后,CBN减少体内肿瘤质量。一起,我们的结果表明CBG，CBC,CBN,和CBDV可以是MM的有前途的抗癌剂。
