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Tumor Biology

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01.04.2014 | Research Article

Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway

verfasst von: Yi Lin, Jianping Xu, Hehe Liao, Lu Li, Lei Pan

Erschienen in: Tumor Biology | Ausgabe 4/2014

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Abstract

The aim of this study was to evaluate the cytotoxic and apoptotic effects of piperine on human lung cancer A549 cells and to explore its mechanisms. Piperine was found to exert the greatest cytotoxic effect against A549 cells in a dose-dependent manner, whereas it showed no effect on WI38 human lung fibroblasts. This cell growth-inhibitory effect might be attributed to cell DNA damage and cytotoxic effects. Besides, piperine had the ability to cause cell cycle arrest in G2/M phase and to activate caspase-3 and caspase-9 cascades in A549 cells. Furthermore, piperine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk in majority. In addition, piperine treatment decreased Bcl-2 protein expression, but increased Bax protein expression in A549 cells, which were positively correlated with an elevated expression of p53 compared to control. Taken together, these results suggested that piperine could induce p53-mediated cell cycle arrest and apoptosis via activation of caspase-3 and caspase-9 cascades, as well as increasing the Bax/Bcl-2 ratio. Thus, piperine could be developed as an effective antitumor agent in the prevention and treatment of lung cancer without toxicity to the host.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–30.PubMedCrossRef

Hung JY, Hsu YL, Ko YC, Tsai YM, Yang CJ, Huang MS, et al. Didymin, a dietary flavonoid glycoside from citrus fruits, induces Fas-mediated apoptotic pathway in human non-small-cell lung cancer cells in vitro and in vivo. Lung Cancer. 2010;68:366–74.PubMedCrossRef

Saba NF, Khuri FR. Chemoprevention strategies for patients with lung cancer in the context of screening. Clin Lung Cancer. 2005;7:92–9.PubMedCrossRef

Ten Bokkel Huinink WW, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen PL, et al. Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer. Lung Cancer. 1999;26:85–94.PubMedCrossRef

Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, et al. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000;18:122–30.PubMed

Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000;18:623–31.PubMed

Chou JY, Lai SY, Pan SL, Jow GM, Chern JW, Guh JH. Investigation of anticancer mechanism of thiadiazole-based compound in human non-small cell lung cancer A549 cells. Biochem Pharmacol. 2003;66:115–24.PubMedCrossRef

Bonomi P. Review of paclitaxel/carboplatin in advanced non-small cell lung cancer. Sem Oncol. 1999;26:55–8.

Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA. 1998;280:1569–75.PubMedCrossRef

10.

Risberg T, Lund E, Wist E, Kaasa S, Wilsgaard T. Cancer patients use of nonproven therapy: a 5-year follow-up study. J Clin Oncol. 1998;16:6–12.PubMed

11.

Chang HC, Hung WC, Huang MS, Hsu HK. Extract from the leaves of Toona sinensis Roemor exerts potent antiproliferative effect on human lung cancer cells. Am J Chin Med. 2002;30:307–14.PubMedCrossRef

12.

Li YM, Ohno Y, Minatoguchi S, Fukuda K, Ikoma T, Ohno T, et al. Extracts from the roots of Lindera strychifolia induces apoptosis in lung cancer cells and prolongs survival of tumor-bearing mice. Am J Chin Med. 2003;31:857–69.PubMedCrossRef

13.

Tuntiwechapikul W, Taka T, Songsomboon C, Kaewtunjai N, Imsumran A, Makonkawkeyoon L, et al. Ginger extract inhibits human telomerase reverse transcriptase and c-Myc expression in A549 lung cancer cells. J Med Food. 2010;13:1347–54.PubMedCrossRef

14.

Reanmongkol W, Janthasoot W, Wattanatorn W, Upakorn PD, Chudapongse P. Effects of piperine on bioenergetics functions of isolated rat liver mitochondria. Biochem Pharmacol. 1988;37:753–7.PubMedCrossRef

15.

Piyachaturawat P, Kingkaeohoi S, Toskulkao C. Potentiation of carbon tetrachloride hepatotoxicity by piperine. Drug Chem Toxicol. 1995;18:333–44.PubMedCrossRef

16.

Nakini N, Sabitha K, Viswanathan P, Menon VP. Spices and glycoproteins metabolism in experimental colon cancer in rats. Med Sci Res. 1998;26:781–4.

17.

Dhuley JN, Raman PH, Mujumda M, Naik SR. Inhibition of lipid peroxidation by piperine during experimental inflammation in rats. Indian J Exp Biol. 1993;31:443–5.PubMed

18.

Rashmeet KR, Jaswant S. In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine. J Exp Biol. 1991;29:568–73.

19.

Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine. Evidence that piperine is a potent inhibitor of drug metabolism. J Pharmacol Exp Ther. 1985;232:258–62.PubMed

20.

Allameh A, Saxena M, Biswas G, Raj HG, Singh J, Srivastava N. Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. Cancer Lett. 1992;61:195–9.PubMedCrossRef

21.

Koul IB, Kapil A. Evaluation of the liver protective potential of piperine, an active principle of black and long peppers. Planta Med. 1993;59:413–7.

22.

Chu CY, Chang JP, Wang CJ. Modulatory effect of piperine on benzo[a]pyrene cytotoxicity and DNA adduct formation in V-79 lung fibroblast cells. Food Chem Toxicol. 1994;32:373–7.PubMedCrossRef

23.

Alleme S (1991) Piperine enchanced the bioavailability of the aflatoxin B1 induced in rat tissues. Cancer Lett 195–9.

24.

Zhang Y, Wang Q, Wang T, Zhang H, Tian Y, Luo H, et al. Inhibition of human gastric carcinoma cell growth in vitro by a polysaccharide from Aster tataricus. Int J Biol Macromol. 2012;51:509–13.PubMedCrossRef

25.

Lee TH, Chuang LY, Hung WC. Tamoxifen induces p21Waf1 and p27Kip1 expression in estrogen receptor-negative lung cancer cells. Oncogene. 1999;18:4269–74.PubMedCrossRef

26.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein binding. Anal Biochem. 1976;72:248–54.PubMedCrossRef

27.

Hung WC, Chuang LY. Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-alpha. Br J Cancer. 1999;80:705–10.PubMedCentralPubMedCrossRef

28.

Enari M, Sakahira H, Yokoyoma H, Okawa K, Iwamtsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 1998;391:43–50.PubMedCrossRef

29.

Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1998;282:1497–501.PubMedCrossRef

30.

Karpinich NO, Tafani M, Rothman RJ, Russo MA, Farber JL. The course of etoposide induced apoptosis from damage to DNA and p53 activation to mitochondrial release of cytochrome c. J Biol Chem. 2002;277:16547–52.PubMedCrossRef

31.

Mercer WE, Shields MT, Amin M, Sauve GJ, Appella E, Romano JW, et al. Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci U S A. 1990;87:6166–70.PubMedCentralPubMedCrossRef

32.

Baker SJ, Markowitz S, Fearon ER, Willson JK, Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990;249:912–5.PubMedCrossRef

33.

Tian Z, Shen J, Moseman AP, Yang Q, Yang J, Xiao P, et al. Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Int J Cancer. 2008;122:31–8.PubMedCrossRef

34.

Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15:269–90.PubMedCrossRef

Titel: Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway
verfasst von: Yi Lin
Jianping Xu
Hehe Liao
Lu Li
Lei Pan
Publikationsdatum: 01.04.2014
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 4/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-1433-4

Springer Medizin

Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway

Abstract

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Springer Medizin

Abstract

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