Emodin promotes the arrest of human lymphoma Raji cell proliferation through the UHRF1-DNMT3A-∆Np73 pathways

Abstract

Emodin is an active constituent found in the roots and rhizomes of numerous Chinese medicinal herbs. It exerts antitumor activity against Dalton's lymphoma in vivo, although the detailed mechanisms by which emodin induces apoptosis remains to be elucidated. The present study aimed to analyze the mechanisms underlying the response to emodin treatment. Using lymphoma Raji cells, an emodin-induced cell proliferating inhibition model was first established, then flow cytometry, western blotting, reverse transcription-quantitative polymerase chain reaction and luciferase reporter assay were performed. It was found that emodin decreased the percentage of Raji cell viability, induced apoptosis, and increased the activation of caspase 3, caspase 9 and poly (ADP-ribose) polymerase through the downregulation of ubiquitin-like protein containing PHD and RING domains 1 (UHRF1). The emodin-induced downregulation of UHRF1 led to an increase in the level of DNA methyltransferase 3A, which in turn inhibited the activity of p73 promoter 2 and decreased the levels of NH2-terminally truncated dominant-negative p73. The treatment of Raji cells with emodin combined with doxorubicin led increased cell death of Raji cells, indicating that emodin may sensitize Raji cells to doxorubicin-induced apoptosis.

Emodin Rescued Hyperhomocysteinemia-Induced Dementia and Alzheimer’s Disease-Like Features in Rats

“…In Panc-1 cells, emodin decreased the methylation levels in the promoter region of several key tumor-suppressor genes by inhibiting the expression of DNMT1 and DNMT3α (Pan et al, 2016). However, in lymphoma Raji cells, emodin inhibited cell proliferation potentially by increasing DNMT3α (Lin et al, 2017). Besides the protein levels, the activities of DNMTs are influenced by several other factors, including local chromatin microenvironments (van der Wijst et al, 2015).…”

Epigenetic mechanism and target therapy of UHRF1 protein complex in malignancies

“…Shikonin134 induces downregulation of both UHRF1 and DNMT1 in MDF-7 and hela cell lines. In addition, hinokitiol,68 dihydroartemisinin,89 epigallocatechin-3-gallate,135 emodin,136 mTOR inhibitor torin-2,137 luteolin,69 ERK1/2 pathway inhibitor PD98059, LY294002, AG490,138 Hsp90 inhibitor 17-AAG or 17-dimethylamino-ethylamino-17-demethoxygeldanamycin,121 anisomycin,139 and curcumin95,140 have been reported to be used in various types of cancers.…”

Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development

“…Emodin is an anthraquinone found in several plants that was previously utilized as a laxative and currently employed as a tool in toxicity studies (PubChem CID: 3220). A recent study reported the role of emodin in promoting the arrest of human lymphoma Raji cell proliferation via the UHRF1-DNMT3A-ΔNp73 pathways [ 93 ]. Emodin was found to downregulate UHRF1, and therefore lead to a decrease in the lymphoma Raji cell viability, induction of apoptosis, and increased the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase.…”