Pseudolaric acid B induces apoptosis in U937 human leukemia cells via caspase-9‑mediated activation of the mitochondrial death pathway

Wang,Jia-He; Kan,Liang; Shu,Lin-Hua; Wang,Nan; Li,Nai-Jing; Zhang,Meng

doi:10.3892/mmr.2013.1571

Pseudolaric acid B induces apoptosis in U937 human leukemia cells via caspase-9‑mediated activation of the mitochondrial death pathway

Authors:
- Jia-He Wang
- Liang Kan
- Lin-Hua Shu
- Nan Wang
- Nai-Jing Li
- Meng Zhang
View Affiliations

Affiliations: Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: July 4, 2013 https://doi.org/10.3892/mmr.2013.1571
Pages: 787-793

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Numerous studies have demonstrated that pseudolaric acid B (PAB) promotes apoptosis in several cancer cell lines. However, thus far, the effect of PAB on human leukemia cells has not been evaluated. In the present study, the antitumor activity and molecular mechanisms of PAB in human leukemia U937 cells were investigated. It was demonstrated that PAB induced U937 cell apoptosis, which was confirmed by typical morphological changes and Annexin V‑fluorescein isothiocyanate staining. PAB was observed to activate a caspase‑dependent apoptotic pathway in U937 cells through the regulation of the Bcl‑2 family protein-mediated mitochondrial pathway. Furthermore, the activities of caspase‑3 and -9 were increased following treatment with PAB. In conclusion, to the best of our knowledge, this study demonstrated for the first time that PAB was able to enhance the apoptosis of U937 cells, at least in part, through the activation of the mitochondrial death pathway. Moreover, the activation of caspase‑3 and -9 mediated the apoptotic induction.

View Figures

View References

1	Ma G, Chong L, Li XC, Khan IA, Walker LA and Khan SI: Selective inhibition of human leukemia cell growth and induction of cell cycle arrest and apoptosis by pseudolaric acid B. J Cancer Res Clin Oncol. 136:1333–1340. 2010. View Article : Google Scholar : PubMed/NCBI
2	Li YC, Tyan YS, Kuo HM, Chang WC, Hsia TC and Chung JG: Baicalein induced in vitro apoptosis undergo caspases activity in human promyelocytic leukemia HL-60 cells. Food Chem Toxicol. 42:37–43. 2004. View Article : Google Scholar : PubMed/NCBI
3	Zhao D, Lin F, Wu X, Zhao Q, Zhao B, Lin P, Zang Y and Yu X: Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells. Toxicol In Vitro. 26:595–602. 2012. View Article : Google Scholar : PubMed/NCBI
4	Kim EJ, Park SY, Lee JY and Park JH: Fucoidan present in brown algae induces apoptosis of human colon cancer cells. BMC Gastroenterol. 10:962010. View Article : Google Scholar : PubMed/NCBI
5	Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobayashi M and Kitagawa I: Inhibition of in vitro tumor cell invasion by ginsenoside Rg3. Jpn J Cancer Res. 87:357–362. 1996. View Article : Google Scholar : PubMed/NCBI
6	Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science. 267:1456–1462. 1995. View Article : Google Scholar : PubMed/NCBI
7	Nicholson DW: From bench to clinic with apoptosis-based therapeutic agents. Nature. 407:810–816. 2000. View Article : Google Scholar : PubMed/NCBI
8	Danial NN and Korsmeyer SJ: Cell death: critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI
9	Kim KN, Ham YM, Moon JY, Kim MJ, Jung YH, Jeon YJ, Lee NH, Kang N, Yang HM, Kim D and Hyun CG: Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia. Food Chem. 135:2112–2117. 2012. View Article : Google Scholar : PubMed/NCBI
10	Du RH, Cui JT, Wang T, Zhang AH and Tan RX: Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway. Toxicon. 59:143–150. 2012. View Article : Google Scholar : PubMed/NCBI
11	Guizzunti G, Theodorakis EA, Yu AL, Zurzolo C and Batova A: Cluvenone induces apoptosis via a direct target in mitochondria: a possible mechanism to circumvent chemo-resistance? Invest New Drugs. 30:1841–1848. 2012. View Article : Google Scholar : PubMed/NCBI
12	Rastogi RP, Singh SP, Häder DP and Sinha RP: Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2′,7′-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochem Biophys Res Commun. 397:603–607. 2010.PubMed/NCBI
13	An J, Gao Y, Wang J, Zhu Q, Ma Y, Wu J, Sun J and Tang Y: Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathway. Biotechnol Lett. 34:1781–1788. 2012. View Article : Google Scholar : PubMed/NCBI
14	Yu JH, Cui Q, Jiang YY, Yang W, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces apoptosis, senescence, and mitotic arrest in human breast cancer MCF-7. Acta Pharmacol Sin. 28:1975–1983. 2007. View Article : Google Scholar : PubMed/NCBI
15	Circu M and Aw TY: Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 48:749–762. 2010. View Article : Google Scholar : PubMed/NCBI
16	Huang C, Chen X, Guo B, Huang W, Shen T, Sun X, Xiao P and Zhou Q: Induction of apoptosis by Icariside II through extrinsic and intrinsic signaling pathways in human breast cancer MCF7 cells. Biosci Biotechnol Biochem. 76:1322–1328. 2012. View Article : Google Scholar : PubMed/NCBI
17	Kroemer G and Reed JC: Mitochondrial control of cell death. Nat Med. 6:513–519. 2000. View Article : Google Scholar
18	Yu JH, Wang HJ, Li XR, Tashiro S, Onodera S and Ikejima T: Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced apoptosis of human breast cancer MCF-7 cells. Acta Pharmacol Sin. 29:1069–1076. 2008. View Article : Google Scholar : PubMed/NCBI
19	Ko JK, Leung WC, Ho WK and Chiu P: Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene. Eur J Pharmacol. 559:1–13. 2007. View Article : Google Scholar : PubMed/NCBI
20	Gong X, Wang M, Wu Z, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces apoptosis via activation of c-Jun N-terminal kinase and caspase-3 in HeLa cells. Exp Mol Med. 36:551–556. 2004. View Article : Google Scholar : PubMed/NCBI
21	Gong XF, Wang MW, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces apoptosis through p53 and Bax/Bcl-2 pathways in human melanoma A375-S2 cells. Arch Pharm Res. 28:68–72. 2005. View Article : Google Scholar : PubMed/NCBI
22	Yu J, Li X, Tashiro S, Onodera S and Ikejima T: Bcl-2 family proteins were involved in pseudolaric acid B-induced autophagy in murine fibrosarcoma L929 Cells. J Pharmacol Sci. 107:295–302. 2008. View Article : Google Scholar : PubMed/NCBI
23	Yim SY, Lee YJ, Lee YK, Jung SE, Kim JH, Kim HJ, Son BG, Park YH, Lee YG, Choi YW and Hwang DY: Gomisin N isolated from Schisandra chinensis significantly induces anti-proliferative and pro-apoptotic effects in hepatic carcinoma. Mol Med Rep. 2:725–732. 2009.PubMed/NCBI
24	Tanaka T, Bai T, Utsunomiya H, Fukumoto T and Yukawa K: STAT3 enhances intracellular Fas-mediated apoptotic signals in HHUA human endometrial epithelial cells. Mol Med Rep. 4:307–312. 2011. View Article : Google Scholar : PubMed/NCBI
25	Jeong JK, Moon MH, Seo JS, Seol JW, Lee YJ and Park SY: Sulforaphane blocks hypoxia-mediated resistance to TRAIL-induced tumor cell death. Mol Med Rep. 4:325–330. 2011.PubMed/NCBI
26	Saraste A and Pulkki K: Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res. 45:528–537. 2000. View Article : Google Scholar
27	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar
28	Schneider-Jakob S, Corazza N, Badmann A, Sidler D, Stuber-Roos R, Keogh A, Frese S, Tschan M and Brunner T: Synergistic induction of cell death in liver tumor cells by TRAIL and chemotherapeutic drugs via the BH3-only proteins Bim and Bid. Cell Death Dis. 1:e862010. View Article : Google Scholar : PubMed/NCBI
29	Qiao SX, Cabello CM, Lamore SD, Lesson JL and Wondrak GT: D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis. Apoptosis. 17:1079–1094. 2012. View Article : Google Scholar
30	Yuan Z, Long C, Junming T, Qihuan L, Youshun Z and Chan Z: Quercetin-induced apoptosis of HL-60 cells by reducing PI3K/Akt. Mol Biol Rep. 39:7785–7793. 2012. View Article : Google Scholar : PubMed/NCBI