J Cancer 2020; 11(16):4907-4916. doi:10.7150/jca.45146

Research Paper

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

Qilin Feng1#, Qingchun Yao2#, Bo Li3#, Yongsheng Xie1, Hui Zhang1, Zhijian Xu3, Kang Lu1, Ke Hu1, Yao Cheng1, Bingqing Shi1, Cheng Huang1, Liping Li1, Xiaosong Wu1, Shanxi You2✉, Jumei Shi1✉, Weiliang Zhu3✉

1. Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
2. Department of Oncology, Taizhou Fourth People's Hospital, Jiangsu 225300, China.
3. CAS Key Laboratory of Receptor Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
#These authors contributed equally to this work.

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Citation:
Feng Q, Yao Q, Li B, Xie Y, Zhang H, Xu Z, Lu K, Hu K, Cheng Y, Shi B, Huang C, Li L, Wu X, You S, Shi J, Zhu W. Glycolysis is suppressed by DCZ0801-induced inactivation of the Akt/mTOR pathway in Multiple Myeloma. J Cancer 2020; 11(16):4907-4916. doi:10.7150/jca.45146. Available from http://www.jcancer.org/v11p4907.htm

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Abstract

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.

Keywords: DCZ0801, multiple myeloma, apoptosis, cell cycle, glycolysis