Denbinobin, a Phenanthrene fromDendrobium nobile, Impairs Prostate Cancer Migration by Inhibiting Rac1 Activity

Abstract

Prostate cancer is the most prevalent type of cancer in the United States. The most common site of prostate cancer metastasis is bone. CXCL12 is preferentially expressed in bone and is targeted by prostate cancer cells, which over-express the receptor for CXCL12, CXCR4. In response to CXCL12 stimulation, Rac1, a GTPase, along with its effectors, regulates actin polymerization to form lamellipodia, which is a critical event for cell migration. Cortactin, an actin-binding protein, is recruited to the lamellipodia and is phosphorylated at tyrosine residues. The phosphorylated cortactin is also involved in cell migration. The inhibition of Rac1 activity using a dominant negative Rac1 impairs lamellipodial protrusion as well as cortactin translocation and cortactin phosphorylation. Denbinobin, a substance extracted from Dendrobium nobile, has anticancer effects in many cancer cell lines. Whether denbinobin can inhibit prostate cancer cell migration is not clear. Here, we report that denbinobin inhibited Rac1 activity. The inhibition of Rac1 activity prevented lamellipodial formation. Cortactin phosphorylation and translocation to the lamellipodia were also impaired, and PC3 cells were unable to migrate. These results indicate that denbinobin prevents CXCL12-induced PC3 cell migration by inhibiting Rac1 activity.

Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management

“…Most of them occur in monomeric form with hydroxy and or methoxy substituted with equally 9,10dihydro phenanthrenes derivatives. Phenanthraquinones (another type of monomeric phenanthrenes), such as denbinobine and moniliformine found in D. nobile and D. moniliforme (46,47). Denbinobine was reported to demonstrate anti-cancer activity on leukemic, prostate cancer and gastric cancer cell (47-49) (Figure 2D).…”

Dendrobium: Sources of Active Ingredients to Treat Age-Related Pathologies

“…Denbinobin, at the concentration of 10 µM, prevents chemokine protein CXCL12-induced prostate cancer (PC-3) cell migration by inhibiting Rac1 activity. The inhibition of Rac1 activity prevented also lamellipodial formation [ 49 ]. Moniliformediquinone, another phenanthrenequinone from D. moniliforme , have been studied for its tumor inhibition in human hormone refractory metastatic prostate cancer (HRMPC).…”

Extensive Metabolic Profiles of Leaves and Stems from the Medicinal Plant Dendrobium officinale Kimura et Migo

“…The special pharmacological actions on gastritis, diabetes, cancer, fatigue, and ageing ranked D. officinale as “the first of the Chinese nine fairy herbs” [3,4,5]. The major bioactive compounds reported in D. officinale include alkaloids, polyphenols, and polysaccharides [2,6,7,8,9,10]. In particular, the key alkaloid, sesquiterpene dendrobine, has been reported as anti-hypertensive, anti-cancer, analgesic, and antipyretic [11,12].…”