In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines

Jing Zheng; Yingyu Chen; Zhihong Zheng; Yanxin Chen; Yujuan Chai; Wenfeng Wang; Tetsuya Asakawa; Jianda Hu

doi:10.1155/2021/6682787

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines

Evid Based Complement Alternat Med. 2021 Jan 25:2021:6682787. doi: 10.1155/2021/6682787. eCollection 2021.

Authors

Jing Zheng¹, Yingyu Chen¹, Zhihong Zheng¹, Yanxin Chen¹, Yujuan Chai², Wenfeng Wang³, Tetsuya Asakawa^{4

5}, Jianda Hu¹

Affiliations

¹ Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
² School of Medical Engineering, Health Science Center, Shenzhen University, Shenzhen, China.
³ Department of Chemistry, Fuzhou University, Fuzhou 350108, China.
⁴ Department of Neurosurgery, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Shizuoka, Japan.
⁵ Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.

Abstract

Background: Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35.

Methods: MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins.

Results: We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent.

Conclusion: The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo.