Cancer: Multiple Myeloma

Action: Down-regulates miR-21 levels through IL6/STAT3

Berberine is known to modulate microRNA (miRNA) levels, although the mechanism for this action is unknown. Luo et al. previously demonstrate that the expression of 87 miRNAs is differentially affected by berberine in multiple myeloma cells. Among 49 miRNAs that are down-regulated, nine act as oncomirs, including miR-21. Integrative analysis showed that 28 of the down-regulated miRNAs participate in tumor protein p53 (TP53) signaling and other cancer pathways. miR-21 is involved in all these pathways, and is one of the most important oncomirs to be affected by berberine in multiple myeloma cells.

They confirmed that berberine down-regulated miRNA-21 expression and significantly up-regulated the expression of programmed cell death 4 (PDCD4), a predicted miR-21 target. Depletion of PDCD4 by short interfering RNA could rescue berberine-induced cytotoxicity in multiple

Results suggest that berberine suppresses multiple myeloma cell growth, at least in part, by down-regulating miR-21 levels possibly through IL6/STAT3. This led to increased PDCD4 expression, which is likely to result in suppression of the p53 signaling pathway.

Source

Luo X, Gu J, Zhu R, et al. Integrative analysis of differential miRNA and functional study of miR-21 by seed-targeting inhibition in multiple myeloma cells in response to berberine. BMC Syst Biol. 2014 Jul 7;8:82. doi: 10.1186/1752-0509-8-82

Cancer: Multiple Myeloma

Action: Triggers hypomethylation

Berberine reduces the proliferation and induces apoptosis in the multiple myeloma cell line, U266.Qing et al., (2014) explored the detailed mechanism by analysing the gene expression profiles in U266 treated with or without berberine. DNMT1 andDNMT3B, encoding for a highly conserved member of the DNA methyltransferases, decreased significantly. Results show that berberine can repress the expression of DNMT1 and DNMT3B, which triggers hypomethylation of TP53 by changing the DNA methylation level and the alteration of p53 dependent signal pathway in human multiple melanoma cell U266.

Source

Qing Y, Hu H, Liu Y, Feng T, Meng W, Jiang L, Sun Y, Yao Y. Berberine induces apoptosis in human multiple myeloma cell line U266 through hypomethylation of p53 promoter. Cell Biol Int. 2014 May;38(5):563-70.

Cancer: Multiple Myeloma

Action: Inhibits interleukin-6, activates of caspase-3 and caspase-9

Muto et al., (2007) show that emodin significantly induces cytotoxicity in the human myeloma cells through the elimination of myeloid cell leukemia 1 (Mcl-1). Emodin inhibited interleukin-6-induced activation of Janus-activated kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3), followed by the decreased expression of Mcl-1. Activation of caspase-3 and caspase-9 was triggered by emodin, but the expression of other antiapoptotic Bcl-2 family members, except Mcl-1, did not change in the presence of emodin. To clarify the importance of Mcl-1 in emodin-induced apoptosis, the Mcl-1 expression vector was introduced into the human myeloma cells by electroporation. Induction of apoptosis by emodin was almost abrogated in Mcl-1-overexpressing myeloma cells as the same level as in parental cells, which were not treated with emodin. In conclusion, emodin inhibits interleukin-6-induced JAK2/STAT3 pathway selectively and induces apoptosis in myeloma cells via down-regulation of Mcl-1, which is a good target for treating myeloma. Taken together, our results show emodin as a new potent anticancer agent for the treatment of multiple myeloma patients.

Source

Muto A, Hori M, Sasaki Y, et al. Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Mol Cancer Ther. 2007 Mar;6(3):987-94.