Naturally occurring triterpenoid compounds have long been used as anti-inflammatory, antimalarial, and insecticidal agents. It has become evident that some of the natural or synthetic triterpenoids have promising clinical potential as both a therapeutic and chemopreventive agent for cancer. However, the molecular basis for the antitumor activity of triterpenoid has yet to be defined. In this study, we show that pristimerin, a natural triterpenoid, induces mitochondrial cell death in human cervical cancer cells and that reactive oxygen species (ROS)-dependent activation of both Bax and poly(ADP-ribose) polymerase-1 (PARP-1) is critically required for the mitochondrial dysfunction. We also showed that c-Jun N-terminal kinase (JNK) is involved in ROS-dependent Bax activation. Treatment of pristimerin induced an increase in intracellular ROS, JNK activation, conformational change, and mitochondrial redistribution of Bax, mitochondrial membrane potential loss, and cell death. The PARP-1 was also found to be activated by pristimerin treatment. An antioxidant, N-acetyl-L-cysteine (NAC), inhibited pristimerin-induced JNK activation, Bax relocalization, and PARP-1 activation, as well as mitochondrial cell death. Moreover, inhibition of JNK clearly suppressed conformational change and mitochondrial translocation of Bax and subsequent mitochondrial cell death but did not affect PARP-1 activation. Inhibition of PARP-1 with 1,5-dihydroxyisoquinoline (DIQ) or with small interfering RNA of PARP-1 significantly attenuated pristimerininduced mitochondrial membrane potential loss and cell death but did not affect JNK activation and Bax relocalization. These results indicate that the natural triterpenoid pristimerin induces mitochondrial cell death through ROS-dependent activation of both Bax and PARP-1 in human cervical cancer cells and that JNK is involved in ROS-dependent Bax activation.
Thus, our results indicate that BRE acts as a potent inhibitor of the biogenesis of H. pylori virulence proteins and decreases the apoptosis of H. pylori-infected cells. Moreover, our results suggest that BRE can be used to exert beneficial effects in patients with gastroduodenal diseases caused by H. pylori.
Osteoporosis is frequently induced following menopause, and bone fractures result in serious problems including skeletal deformity, pain, and increased mortality. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aimed to clarify the bone protecting effects of germinated soy germ extracts (GSGE) and their mode of action. GSGE increased expression of alkaline phosphatase (ALP) and osteocalcin (OCL) by stimulating the expression of runt-related transcription factor 2 (Runx2) and osterix (Osx) through activation of Smad signaling molecules. Furthermore, germination of soy germ increased levels of nutritional components, especially soyasaponin Ab. The anabolic activity of soyasaponin Ab in GSGE was also evaluated. GSGE and soyasaponin Ab significantly protected against ovariectomy (OVX)-induced bone loss and improved bone-specific alkaline phosphatase (BALP) level in mouse serum. These in vitro and in vivo study results demonstrated that GSGE and soyasaponin Ab have potential as therapeutic candidate agents for bone protection in postmenopausal osteoporosis.
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