Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines

Abstract

Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G1 phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (Δψm) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia.

Antiproliferative Effect and the Isolated Compounds ofPouzolzia indica

“…Previously, the cytotoxicity of 28-hydroxy-3-friedelanone against A549-human lung cancer cell line, LLC-mouse Lewis lung carcinoma, HL60-human promyelocytic cell line, and MCF7-human breast cancer cell line were demonstrated. Hence, some triterpenes could strongly induce apoptosis by attending the mitochondrial membrane potential and regulating the expression of Bcl-2 different compasses [14, 20]. The IC 50 ( μ g/mL) of 7-methoxy-coumarin 3 on HL60 and K562 human chronic leukemia cells was also demonstrated with the values of 28.9 and 19.3  μ g/mL, respectively [21, 22].…”

Acute and Subacute Oral Toxicity Evaluation of Eriobotrya japonica Leaf Triterpene Acids in ICR Mice

“…Eriobotrya japonica leaf is included in the Chinese Pharmacopoeia [1] and widely used as a medicinal material in traditional treatment of a variety of chronic diseases in China and other East Asian countries [2]. Phytochemical investigations showed that its main components are essential oil, triterpenes, sesquiterpenes, flavonoids, tannins, and megastigmane glycosides [3].…”

<b>Triterpenes suppress octanoylated ghrelin production in ghrelin-expressing human gastric carcinoma </b><b>cells </b>

“…PCR was carried out on a 7900HT Fast Real-Time PCR System (Applied Biosystems/Life Technologies, Carlsbad, CA, USA). The reaction mixture containing 10 μL of 2 × Fast SYBR Green Master Mix, 0.4 pmol sense and antisense primers, and 2 μL diluted cDNA (17) was loaded onto a 386-well plate; amplification was carried out under the following conditions: 95°C for 20 s, followed by 40 cycles of 95°C for 1 s and 60°C for 20 s. The following sense and antisense primers were used: human GOAT, 5′-ACAGCTCGA Triterpenes are phytochemicals consisting of six isoprene units that have anti-oxidant, anti-inflammatory, and anti-proliferative effects (2,22,24). Certain triterpenes such as asiatic acid, betulinic acid, corosolic acid, glycyrrhetinic acid, oleanolic acid, and ursolic acid have shown anti-obesity effects in mice fed a high-fat-diet (4,5,18,19,23,25).…”