Preparation of yuanhuacine and relative daphne diterpene esters from Daphne genkwa and structure–activity relationship of potent inhibitory activity against DNA topoisomerase I

The Chinese Herb Isolate Yuanhuacine (YHL-14) Induces G2/M Arrest in Human Cancer Cells by Up-regulating p21 Protein Expression through an p53 Protein-independent Cascade

“…Yuanhuacine (YHL-14), a compound of daphne diterpene ester, is the principal active component of the flowers of D. genkwa. YHL-14 has recently been reported to exhibit potent antiproliferative activity in various cancer cell lines (10,29,30), and this inhibition is associated with its targeting of topoisomerase-DNA complexes and blocking of the regulation step, thereby enhancing the formation of persistent DNA breaks and further leading to cell death. YHL-14 is, therefore, considered to be a DNA-damaging agent (31).…”

“…p38 activation has also been reported to mediate activation and expression of various downstream targets, including transcription factors (ATF2, Sp1, Mac, and MEF2), protein kinases (MAPKAPK2), and cell cycle control proteins (cyclin D1) (44,46). Previous studies have reported that YHL-14 treatment inhibits the relaxation activity of Topo I toward DNA and induces DNA damage in 30 min (10). DNA damage could immediately activate p38 (47,48).…”

Daphnane diterpene esters isolated from flower buds of Daphne genkwa induce apoptosis in human myelocytic HL-60 cells and suppress tumor growth in Lewis lung carcinoma (LLC)-inoculated mouse model

“…In these plants, daphnane diterpene esters appear to be noteworthy, in that they were determined to exert anti-tumoric effects against P-388 (mouse lymphocytic leukemia), A-549 (human lung adenocarcinoma), and HMEC (human microvascular endothelial cell) (Zhan et al, 2005) and L-1210 (mouse lymphocytic leukemia), and KB (epidermoid carcinoma of the mouth) cells (Hall et al, 1986) in vitro, and antileukemic effects (Huai et al, 1985) in vivo. The cytotoxic activity of these compounds was attributed to the suppression of DNA synthesis (Hall et al, 1986;Zhang et al, 2006). However, no mechanistic studies have thus far been conducted in order to determine whether this cytotoxicity occurred via an apoptotic process.…”

Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds

“…One of the best known classes of 54 multi-targeted anti-cancer agents, acridine derivatives act by 55 interfering with DNA synthesis and by inhibiting topoisomerases. 56 The development of DNA topoisomerase inhibitors as cancer 57 chemotherapeutic agents is currently an active area of research 58 (Denny, 2002;Di Giorgio et al, 2008;Oppegard et al, 2009;59 Goodell et al, 2008;Zhang et al, 2006;Lang et al, 2013;Lafayette 60 et al, 2013;Li et al, 2014). 61 Topoisomerases (Topo) are responsible for controlling the 62 topology of DNA and play critical roles in DNA metabolism 63 (Champoux, 2001;Wang, 2002;Vos et al, 2011).…”