Diallyl disulfide synergizes with melphalan to increase apoptosis and DNA damage through elevation of reactive oxygen species in multiple myeloma cells.

Autor: Hu W; 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., Sun J; 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., Zhang Y; 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., Chen T; 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., He F; 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., Zhao H; 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., Tan W; 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., Wang Z; 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., Ouyang J; 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., Tang Z; 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., He J; 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., Wang J; 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., Li J; Department of Hematology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China. hylijunjun@163.com., Zeng X; 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. xzeng@usc.edu.cn., Xia J; 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. jiliang-xia@usc.edu.cn.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Apr; Vol. 103 (4), pp. 1293-1303. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1007/s00277-023-05592-w
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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