Rhabdastrellic acid‐A inhibited PI3K/Akt pathway and induced apoptosis in human leukemia HL‐60 cells

Abstract

Increasing evidence suggests that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer treatment. Our investigation indicates that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge, Rhabdastrella globostellata, inhibits proliferation of HL-60 cells with an IC(50) value of 0.68mug/ml, and induces apoptosis. Rhabdastrellic acid-A also induces cleavage of the death substrate poly (ADP-ribose) polymerase (PARP) and caspase-3. Pretreatment of HL-60 cells with the caspase-3 specific inhibitor, DEVD-CHO, prevents Rhabdastrellic acid-A-induced DNA fragmentation and PARP cleavage. Activated PI3K and Akt significantly decreases after treatment with Rhabdastrellic acid-A in HL-60 cells. Expression levels of protein bcl-2, bax remain unchanged in response to Rhabdastrellic acid-A treatment in HL-60 cells. These results suggest that Rhabdastrellic acid-A inhibits PI3K/Akt pathway and induces caspase-3 dependent-apoptosis in HL-60 human leukemia cells.

Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells

“…Other isomalabaricane triterpenoids were found to induce reactive oxygen species (ROS), decrease mitochondrial membrane potential, increase the levels of Bax and cytochrome c, decrease the levels of Bcl-2 and mediate a caspases-3 apoptotic pathway, but the molecular mechanisms responsible for triterpenoids-induced cell death have not been elucidated yet[5]. Also, our investigation showed that Rhabdastrellic acid-A induced apoptosis in HL-60 cells [4], but the development of apoptotic features in Hep3B and A549 cells following exposure to Rhabdastrellic acid-A was not observed.…”

“…1), an isomalabaricane triterpenoid, was isolated from the yellow sponge Rhabdastrella globostellata (Carter) collected from the South China Sea near Hainan Island, People's Republic of China. Its structure was established on the basis of UV, IR, MS, 1 H-NMR, 13 C-NMR, and 2D NMR spectrometry [3], [4]. The relative and absolute stereochemistries were solved by NOESY and CD studies, respectively.…”

Bioactive Sesterterpenes and Triterpenes from Marine Sponges: Occurrence and Pharmacological Significance

“…together with stelletins E ( 60 ) and F ( 61 ) [78]. The E isomer of stelletin G ( 62 ) was isolated from the marine sponge Rhabdastrella globostellata collected from the South China Sea and it was given the trivial name rhabdastrellic acid–A ( 63 ) [75,76]. …”

“…Stelletins L ( 70 ) and M ( 71 ) exhibited selective cytotoxicity against stomach cancer AGS cells with IC 50 values of 3.9 and 2.1 μM, respectively [85]. Rhabdastrellic acid–A ( 63 ) also inhibited proliferation of human leukemia HL-60 cells with an IC 50 value of 1.5 μM through inhibition of the PI3K/Akt pathway and induction of caspase-3 dependent-apoptosis [76]. Only rhabdastrellin A ( 64 ) possessed moderate inhibitory activity toward human leukemia HL-60 cells (IC 50 = 8.7 μM) while other rhabdastrellins were inactive (IC 50 > 20 μM) [86].…”

Induction of T helper 1 response by immunization of BALB/c mice with the gene encoding the second subunit ofEchinococcus granulosusantigen B (EgAgB8/2)

“…Conversely, induction of a Th1 response may lead to protection against successful parasite establishment. This can be achieved by vaccination with appropriate parasite antigens using specific immunization routes (Al-Qaoud et al , 2008; Ding et al , 2008). Recently, DNA vaccination to viruses, bacteria and parasites has been used as a tool to study the effects of the immunization route (parenteral, intranasal, oral, intralymphatic and intrahepatic) on the immune response (Fynan et al , 1993; Chen, 1998; Sasaki et al , 1998; Maloy et al , 2001; Cruz-Revilla et al , 2006).…”