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

by Selleckchem | Feb 12 2024

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.

Comments:

The research you're referring to sounds quite promising! Diallyl disulfide (DADS), a compound found in garlic, displaying potential anticancer effects in multiple cancers and particularly its impact on multiple myeloma (MM) cells, is intriguing.

The study's findings regarding DADS inducing apoptosis in MM cells through the mitochondria-dependent pathway and increasing DNA damage, as indicated by elevated γ-H2AX levels, are significant. Moreover, the observed synergistic effect between DADS and melphalan, a commonly used anti-MM drug, is particularly noteworthy.

The combination of DADS with melphalan demonstrating a significant increase in apoptotic cells and DNA damage in MM cells compared to individual drug treatments is a strong indicator of their cooperative effect. Additionally, the study's validation of this synergy in primary MM cells reinforces the potential clinical relevance of this combination.

The mechanistic insights revealing DADS' impact on reducing glutathione (GSH) levels while elevating reactive oxygen species (ROS) production in MM cells provide a clearer understanding of how DADS exerts its cytotoxic effects. The observation that GSH addition neutralizes DADS' cytotoxicity and inhibits the synergy with melphalan further solidifies the role of ROS and GSH in this combined treatment's efficacy.

Overall, these findings suggest a promising avenue for MM treatment by combining DADS with melphalan. This research not only underscores the effectiveness of DADS as a potential therapeutic agent for MM but also highlights the importance of exploring combination treatments involving natural compounds like DADS with conventional anti-cancer drugs for enhanced efficacy.