Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Changshengxi Road 28#, Hengyang, 421001, Hunan, China.
Department of Hematology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Ann Hematol. 2024 Apr;103(4):1293-1303. doi: 10.1007/s00277-023-05592-w. Epub 2023 Dec 27.
Diallyl disulfide (DADS), one of the main components of garlic, is well known to have anticancer effects on multiple cancers. However, its efficacy in treating multiple myeloma (MM) is yet to be determined. We explored the effects of DADS on MM cells and investigated the synergistic effects of DADS when combined with five anti-MM drugs, including melphalan, bortezomib, carfilzomib, doxorubicin, and lenalidomide. We analyzed cell viability, cell apoptosis, and DNA damage to determine the efficacy of DADS and the drug combinations. Our findings revealed that DADS induces apoptosis in MM cells through the mitochondria-dependent pathway and increases the levels of γ-H2AX, a DNA damage marker. Combination index (CI) measurements indicated that the combination of DADS with melphalan has a significant synergistic effect on MM cells. This was further confirmed by the increases in apoptotic cells and DNA damage in MM cells treated with the two drug combinations compared with those cells treated with a single drug alone. The synergy between DADS and melphalan was also observed in primary MM cells. Furthermore, mechanistic investigations showed that DADS decreases reduced glutathione (GSH) levels and increases reactive oxygen species (ROS) production in MM cells. The addition of GSH is effective in neutralizing DADS cytotoxicity and inhibiting the synergy between DADS and melphalan in MM cells. Taken together, our study highlights the effectiveness of DADS in treating MM cells and the promising therapeutic potential of combining DADS and melphalan for MM treatment.
二烯丙基二硫醚（DADS）是大蒜中的主要成分之一，已被证实对多种癌症具有抗癌作用。然而，其在多发性骨髓瘤（MM）治疗中的疗效尚待确定。我们研究了 DADS 对 MM 细胞的影响，并探讨了 DADS 与五种抗 MM 药物（包括美法仑、硼替佐米、卡非佐米、阿霉素和来那度胺）联合使用的协同效应。我们分析了细胞活力、细胞凋亡和 DNA 损伤，以确定 DADS 及其药物组合的疗效。我们的研究结果表明，DADS 通过线粒体依赖性途径诱导 MM 细胞凋亡，并增加 DNA 损伤标志物 γ-H2AX 的水平。组合指数（CI）测量表明，DADS 与美法仑联合使用对 MM 细胞具有显著的协同作用。与单独使用单一药物相比，用两种药物组合处理的 MM 细胞中凋亡细胞和 DNA 损伤的增加进一步证实了这一点。DADS 和美法仑之间的协同作用也在原发性 MM 细胞中观察到。此外，机制研究表明，DADS 降低 MM 细胞中的还原型谷胱甘肽（GSH）水平并增加活性氧（ROS）的产生。添加 GSH 可有效中和 DADS 的细胞毒性，并抑制 DADS 和美法仑在 MM 细胞中的协同作用。综上所述，我们的研究强调了 DADS 治疗 MM 细胞的有效性，以及将 DADS 和美法仑联合用于 MM 治疗的有前途的治疗潜力。
