DCZ0801, a novel compound, induces cell apoptosis and cell cycle arrest via MAPK pathway in multiple myeloma

Zhang, Ting; Li, Bo; Feng, Qilin; Xu, Zhijian; Huang, Cheng; Wu, Huiqun; Chen, Zhangbo; Hu, Liangning; Liu, Peng; Yang, Guang; Zhang, Hui; Lu, Kang; Li, Tingye; Yi, Tao; Wu, Xiaosong; Shi, Jumei; Zhu, Weiliang

doi:10.1093/abbs/gmz033

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…Anticancer drugs interfere cell cycle distribution, resulting in arrest of cell cycle phase and induction of apoptotic cell death (Kitai, Zhang, Hayashida, Kakehi, & Tamura, 2017;Zhang et al 2019). Therefore, to further understand whether or not the combination of ATRA and BDMC treatment showed lower cell viability through the cell cycle arrest and cell apoptosis in Hep 3B cells.…”

Section: Discussionmentioning

confidence: 99%

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

et al. 2019

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The effects of two-drug combination, all-trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC), on apoptosis induction of liver cancer cells were investigated in human liver Hep 3B cells. Two-drug combination caused a more effective decrease in cell viability and in induction of S phase arrest, DNA damage, and cell apoptosis than that of ATRA or BDMC only. Also, the two-drug combination caused more cells to undergo significantly increased ROS productions when compared to that of ATRA or BDMC only. Results of Western blotting demonstrated that two-drug combination increased expressions of Fas, pro-apoptotic proteins, and active form of caspase-3 and -9, but decreased that of anti-apoptotic proteins and XIAP than that of ATRA or BDMC only in Hep 3B cells. In conclusion, ATRA combined with BDMC enhance cell apoptosis and associated protein expression in Hep 3B cells. Practical applicationsBisdemethoxycurcumin (BDMC) derived from natural plants, turmeric (Curcuma longa), which had been used for Asia food for thousands of years. All-trans retinoid acid (ATRA) is currently used as a primary treatment for patients with acute

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Section: Discussionmentioning

confidence: 99%

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

et al. 2019

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“…We also observed the effect of DCZ0801 on myeloma primary cells and normal human peripheral blood mononuclear cells, and found that DCZ0801 can induce apoptosis in CD138 + myeloma cells isolated from the bone marrow mononuclear cells of myeloma patients ( Figure 2B). On the contrary, a research showed that no significant cytotoxicity to normal human peripheral blood mononuclear cells was observed at the same dose [35]. This shows that DCZ0801 has a selective killing effect between myeloma cells and normal cells.…”

Section: Dcz0801 Can Induce Apoptosis In MM Cellsmentioning

confidence: 95%

“…DCZ0801 is a synthetic small molecule compound with a molecular weight of 529.48 ( Figure 1A), mentioned in a previous article by our research group [35]. To determine whether DCZ0801 has antimyeloma activity, MM cells were exposed to different concentrations of DCZ0801 (15-180 μM) for 48 h and cell viability was then determined using the CCK-8 assay.…”

Section: Dcz0801 Inhibits the Survival And Proliferation Of Multiple mentioning

confidence: 99%

Glycolysis is suppressed by DCZ0801-induced inactivation of the Akt/mTOR pathway in Multiple Myeloma

Feng

Yao

et al. 2020

J. Cancer

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Multiple myeloma (MM) is a highly invasive and incurable plasma cell malignant disease with frequent recurrence. DCZ0801 is a natural compound synthesized from osalmide and pterostilbene and has few adverse effects. Here, we aimed to observe the therapeutic effects of DCZ0801 on myeloma cells and clarify the specific molecular mechanism underlying its anti-tumor activity. The Cell Counting Kit-8 assay, apoptosis detection, cell cycle analysis, western blot analysis, and tumor xenograft models were used to determine the effect of DCZ0801 treatment both in vivo and in vitro. We revealed that DCZ0801 treatment suppressed MM cell survival by inducing apoptosis and blocking the cell cycle at S phase. Deranged glycolysis and downregulated Akt/mTOR pathway may also be responsible for cell proliferation inhibition. Moreover, DCZ0801 treatment could remarkably reduce the tumor size in the xenograft mouse model. Therefore these findings indicate that DCZ0801 can be used as a novel therapeutic drug for patients suffering from multiple myeloma.

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“…11 In our previous study, we also found that a compound that consisted of oxophenamide and pterostilbene showed excellent antitumor effects on multiple myeloma. 12 As shown in Fig. 1a, DCZ0858 is a novel silicone derivative of natural osalmid with a molecular weight of 385.535 Da.…”

Section: Dcz0858 Inhibits Dlbcl Cell Growth and Proliferationmentioning

confidence: 99%

A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway

Zhang

et al. 2020

Sig Transduct Target Ther

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Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor characterized by diffuse growth. DCZ0858 is a novel small molecule with excellent antitumor effects in DLBCL. This study explored in depth the inhibitory effect of DCZ0858 on DLBCL cell lines. Cell Counting Kit-8 (CCK-8) and plate colony formation assays were used to evaluate cell proliferation levels. Flow cytometry was employed to analyze apoptosis and the cell cycle, and western blotting was used to quantify the expression of cell cycle regulators. The results indicated that DCZ0858 inhibited cell growth in a concentration-dependent and time-dependent manner while inducing no significant toxicity in normal cells. Moreover, DCZ0858 initiated cell apoptosis via both internal and external apoptotic pathways. DCZ0858 also induced cell cycle arrest in the G0/G1 phase, thereby controlling cell proliferation. Further investigation of the molecular mechanism showed that the JAK2/STAT3 pathway was involved in the DCZ0858-mediated antitumor effects and that JAK2 was the key target for DCZ0858 treatment. Knockdown of JAK2 partly weakened the DCZ0858-mediated antitumor effect in DLBCL cells, while JAK2 overexpression strengthened the effect of DCZ0858 in DLBCL cells. Moreover, a similar antitumor effect was observed for DCZ0858 and the JAK2 inhibitor ruxolitinib, and combining the two could significantly enhance cancer-suppressive signaling. Tumor xenograft models showed that DCZ0858 inhibited tumor growth in vivo and had low toxicity in important organs, findings that were consistent with the in vitro data. In summary, DCZ0858 is a promising drug for the treatment of DLBCL.

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DCZ0801, a novel compound, induces cell apoptosis and cell cycle arrest via MAPK pathway in multiple myeloma

Cited by 10 publications

References 24 publications

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

Glycolysis is suppressed by DCZ0801-induced inactivation of the Akt/mTOR pathway in Multiple Myeloma

A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway

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