Sesquiterpene lactones derived from Saussurea lappa induce apoptosis and inhibit invasion and migration in neuroblastoma cells

Abstract

Neuroblastoma is among the most fatal of solid tumors in the pediatric age group, even when treated aggressively. Therefore, a new effective therapeutic drug(s) for neuroblastoma is urgently needed. To clarify the anticancer effects of the sesquiterpene lactones dehydrocostus lactone and costunolide, derived from Saussurea lappa, we examined the cytotoxic and migration/invasion-inhibitory effects of these compounds against neuroblastoma cell lines. Both the compounds exerted significant cytotoxicity against the neuroblastoma cell lines IMR-32, NB-39, SK-N-SH, and LA-N-1. Evidence of cellular apoptosis, such as nuclear condensation and membrane inversion, were observed after treatment with these compounds. Both compounds induced caspase-7 activation and PARP cleavage as confirmed by Western blotting. Furthermore, the sesquiterpene lactones also suppressed invasion and migration of the neuroblastoma cells. These results suggest that dehydrocostus lactone and costunolide are promising candidates for being developed into novel anticancer drugs effective against neuroblastoma.

Dehydrocostus lactone inhibits in vitro gastrinoma cancer cell growth through apoptosis induction, sub-G1 cell cycle arrest, DNA damage and loss of mitochondrial membrane potential

“…Our studies are also consistent with previous studies wherein sesquiterpene lactones have been reported to exhibit anticancer activities against a range of cancer types [7]. It has also been reported that these lactones exhibit selective cytotoxic activity against cancer cells and exhibit high IC 50 values for normal cell lines indicating lower cytotoxicity for normal cells [8]. Moreover, to evaluate the effect of the solvent, we determined the cytotoxic effects of DMSO on BON-1 and the results indicated that DMSO had negligible antiproliferative effects (Figure 8).…”

“…The results of this experiment indicated that as compared to the untreated control which did not show any signs of DNA fragmentation, dehydrocostus lactone treated cells at increasing doses indicated significant levels of DNA fragmentation. Consistent with this, several studies have reported induction of apoptosis by dehydrocostus lactone and costunolide in many types of cancer cells [7][8][9].…”

Parthenolide promotes apoptotic cell death and inhibits the migration and invasion of SW620 cells

“…Codonolactone also attenuated transforming growth factor-β1-mediated EMT and motility of breast cancer cells 31. Moreover, it has been reported that costunolide, derived from Saussurea lappa , induces apoptosis and inhibits cell migration and invasion in neuroblastoma cells 32. To date, only two studies have demonstrated that PT suppresses cell migration and invasion in human cancer cells.…”

Dehydrocostus lactone, a naturally occurring polar auxin transport inhibitor, inhibits epicotyl growth by interacting with auxin in etiolated Pisum sativum seedlings

“…AUX1 and PINs have been demonstrated to play important roles in polar auxin transport as an influx and efflux carriers, respectively [4,[11][12][13][44][45][46][47]. In etiolated pea seedlings, PsAUX1 and PsPIN1, PsPIN2 and PsPIN3 have been isolated [27][28][29][30][31][32][33][34][35][36][37][38][39]46,47]. Semiquantitative RT-PCR analysis revealed that DHCL substantially reduced accumulation of mRNA both of PsAUX1 and PsPIN1 in the etiolated pea seedlings (Fig.…”

“…A number of germacranolide-type sesquiterpene lactones with an α-methylene-γlactone derivatives obtained from natural sources have been demonstrated to exhibit pharmaceutically interesting biological activities in animals and plants. DHCL and costunolide have been demonstrated to show antitumor activity, anti-inflammatory activity, and the induction of apoptosis [26][27][28][29][30][31][32]. These compounds are also demonstrated to act as germination stimulants for the root parasitic broomrapes Orobanche cumana Wallr.…”