icaritin and Multiple-Myeloma

Topics: Biological Products; Cell Proliferation; Epimedium; Flavonoids; Hematologic Neoplasms; Humans; Leukemia; Lymphoma; Medicine, Chinese Traditional; Multiple Myeloma

Icaritin has potential anticancer effects on various cancers, including multiple myeloma (MM). Recent studies claim that Icaritin can regulate the expression of noncoding RNAs (ncRNAs) in cancer development. This study aimed to investigate the role of circular RNA_0000190 (circ_0000190) and functional mechanism in Icaritin-treated MM. The expression of circ_0000190 and miR-301a was detected by quantitative real-time polymerase chain reaction. Cell cycle, apoptosis, migration, and invasion were investigated using flow cytometry assay, and transwell assay, respectively. The expression of BAX, BCL2, MMP2, and CCND1 was detected by western blot. The predicted target relationship between circ_0000190 and miR-301a was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The activation of JAK1/STAT3 pathway was examined using western blot. Circ_0000190 was strikingly downregulated in MM specimens and cell lines, and Icaritin promoted the expression of circ_0000190. In function, circ_0000190 overexpression promoted MM cell cycle arrest and apoptosis but restrained the ability of migration and invasion. Icaritin blocked the development of MM by increasing circ_0000190 expression. MiR-301a was identified as a target of circ_0000190, and miR-301a reintroduction largely abolished the effects of circ_0000190 overexpression. The activation of JAK1/STAT3 pathway was promoted by miR-301a restoration. Icaritin played anticancer effects in MM partly by enhancing the expression of circ_0000190 and regulating the circ_0000190/miR-301a pathway. This study enhanced the understanding of the mechanism of Icaritin associated with circRNAs in MM.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Multiple Myeloma; RNA, Circular

Icaritin is an active ingredient in

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Epimedium; Flavonoids; Humans; Intracellular Signaling Peptides and Proteins; Molecular Structure; Multiple Myeloma; Structure-Activity Relationship

To investigate the reversing effect of icaritin on multidrug resistance of multiple myeloma cell lines KM3/BTZ and its underlying mechanism.. KM3/BTZ cells were established by a gradually ascending gradient induction of bortezomib (BTZ). The sensitivities of KM3 and KM3/BTZ cells to 7 chemotherapeutic drugs, the inhibition and reversal effects of icaritin on proliferation and drug-resistance of KM3/BTZ cells were analyzed by MTT. The apoptosis was analyzed by flow cytometry, and the expression of Par-4, HSP27 and P-gp were detected by Western blot.. Icaritin can inhibit cell proliferation and induce apoptosis of KM3/BTZ cells, moreover, can effectively reverse the multidrug resistance of KM3/BTZ cells. The mechanism may be related with down-regulation of HSP27 and P-gp expression, and up-regulation of Par-4 expression.

Topics: Antineoplastic Agents; Apoptosis; Bortezomib; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Flavonoids; Humans; Multiple Myeloma

Icaritin is an active prenylflavonoid derived from Epimedium genus, a traditional Chinese medicine. Icaritin has a wide range of pharmacological and biological activities, including cardiovascular function improvement, hormone regulation and antitumor activity. Here, we investigated the effect of icaritin on multiple myeloma (MM) in vitro and in vivo. Icaritin inhibited cell growth of MM cell line and primary MM cells. In contrast, icaritin had low or no cytotoxic effect on normal hematopoiesis. We also demonstrated that in MM xenograft mouse models, icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did not show adverse reactions such as body weight loss. The anti-MM activity of icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. We suggest that icaritin can be further tested in clinical trials in MM.

Topics: Animals; Female; Flavonoids; Humans; Interleukin-6; Janus Kinase 2; Mice; Mice, Inbred NOD; Mice, SCID; Multiple Myeloma; STAT3 Transcription Factor; Xenograft Model Antitumor Assays