and a passenger strand (termed miRNA*) that was initially believed
to be non-functional in most cases and to be degraded soon.
However, the passenger strand leading to miR-21* (¼miR-21-3p)
plays an important role for the regulation of cell growth as well. In
hepatocellular carcinoma cells (HepG2), berberine increased the
levels of miR-21-3p associated with tumor growth inhibition and
apoptosis induction [83]. It was shown that miR-21-3p acted as a
tumor suppressor in the hepatoma cells and directly inhibited the
expression of the methionine adenosyltransferases MAT2A and
MAT2B accompanied by increased SAM (S-adenosyl-methionine)
levels as a mechanism of the anti-hepatoma activity of miR-21-3p
and berberine [83]. Berberine also significantly suppressed the
miRNA clusters miR-99a~125b, miR-17e92 and miR-106e25 in
multiple myeloma cells [84]. In particular, downregulation of the
oncogenic miR-99a~125b cluster by berberine (mediated by modulation
of p53, Erb and MAPK signaling pathways) induced
apoptosis and cell cycle arrest in the G2-phase in multiple myeloma
cells [84].
Palmatine features another isoquinoline alkaloid of the roots of
Coptis japonica whose chemical structure is closely related to
berberine (Fig. 5) [85]. Palmatine revealed anticancer activity
against prostate cancer cells by inhibition of NF-kB [86]. In breast
cancer cells (MCF-7), the expression of the tumor suppressor miR-
200c was increased after treatment with palmatine chloride leading
to ZEB1 inhibition and E-cadherin upregulation [87]. In addition,
palmatine chloride induced the expression of the tumor
suppressors miR-34a and miR-141 in MCF-7 breast cancer cells
[87].
The quinolizidine alkaloid matrine was isolated from Sophora
flavescens and exhibited strong anticancer activity (Fig. 5) [88]. In
breast cancer cells, matrine induced cell cycle arrest and apoptosis