BMC Complementary and Alternative Medicine | |
Crude aqueous extracts of Pluchea indica (L.) Less. inhibit proliferation and migration of cancer cells through induction of p53-dependent cell death | |
Yi-Ren Hong2  Li-Jen Liao5  Ya-Zhe Lee6  Chao-Neng Tseng1  Chien-Ming Chen6  Chiu-Li Kao4  Chung-Lung Cho6  Jonathan J Cho3  | |
[1] Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan;Department of Biochemistry, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;Department of Biology, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA;Tzu Hui Institute of Technology, Pingtung County, Taiwan;Department of Biotechnology, National Kaohsiung Normal University, Kaohsiung, Taiwan;Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan | |
关键词: Apoptosis; Cell growth arrest; p21; p53; Cancer; Crude aqueous extracts; Pluchea indica (L.) Less; | |
Others : 1231301 DOI : 10.1186/1472-6882-12-265 |
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received in 2012-02-29, accepted in 2012-11-30, 发布年份 2012 | |
【 摘 要 】
Background
Pluchea indica (L.) Less. (Asteraceae) is a perennial shrub plant with anti-inflammatory and antioxidant medicinal properties. However, the anti-cancer properties of its aqueous extracts have not been studied. The aim of this study was to investigate the anti-proliferation, anti-migration, and pro-apoptotic properties of crude aqueous extracts of P. indica leaf and root on human malignant glioma cancer cells and human cervical cancer cells, and the underlying molecular mechanism.
Methods
GBM8401 human glioma cells and HeLa cervical carcinoma cells were treated with various concentrations of crude aqueous extracts of P. indica leaf and root and cancer cell proliferation and viability were measured by cell growth curves, trypan blue exclusions, and the tetrazolium reduction assay. Effects of the crude aqueous extracts on focus formation, migration, and apoptosis of cancer cells were studied as well. The molecular mechanism that contributed to the anti-cancer activities of crude aqueous extracts of P. indica root was also examined using Western blotting analysis.
Results
Crude aqueous extracts of P. indica leaf and root suppressed proliferation, viability, and migration of GBM8401 and HeLa cells. Treatment with crude aqueous extracts of P. indica leaf and root for 48 hours resulted in a significant 75% and 70% inhibition on proliferation and viability of GBM8401 and HeLa cancer cells, respectively. Crude aqueous extracts of P. indica root inhibited focus formation and promoted apoptosis of HeLa cells. It was found that phosphorylated-p53 and p21 were induced in GBM8401 and HeLa cells treated with crude aqueous extracts of P. indica root. Expression of phosphorylated-AKT was decreased in HeLa cells treated with crude aqueous extracts of P. indica root.
Conclusion
The in vitro anti-cancer effects of crude aqueous extracts of P. indica leaf and root indicate that it has sufficient potential to warrant further examination and development as a new anti-cancer agent.
【 授权许可】
2012 Cho et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348(6):518-527.
- [2]Wrensch M, Minn Y, Chew T, Bondy M, Berger MS: Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 2002, 4(4):278-299.
- [3]Smith RR, Malmgren RA: Cancer-cell wound seeding in surgery: a review. CA Cancer J Clin 1964, 14:90-103. PASSIM
- [4]Timmerman RD, Bizekis CS, Pass HI, Fong Y, Dupuy DE, Dawson LA, Lu D: Local surgical, ablative, and radiation treatment of metastases. CA Cancer J Clin 2009, 59(3):145-170.
- [5]Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ: Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 2010, 60(3):166-193.
- [6]Cassileth BR: Evaluating complementary and alternative therapies for cancer patients. CA Cancer J Clin 1999, 49(6):362-375.
- [7]Sparreboom A, Cox MC, Acharya MR, Figg WD: Herbal remedies in the united states: potential adverse interactions with anticancer agents. J Clin Oncol 2004, 22(12):2489-2503.
- [8]Bardia A, Barton DL, Prokop LJ, Bauer BA, Moynihan TJ: Efficacy of complementary and alternative medicine therapies in relieving cancer pain: a systematic review. J Clin Oncol 2006, 24(34):5457-5464.
- [9]Boon H, Stewart M, Kennard MA, Gray R, Sawka C, Brown JB, McWilliam C, Gavin A, Baron RA, Aaron D, et al.: Use of complementary/alternative medicine by breast cancer survivors in ontario: prevalence and perceptions. J Clin Oncol 2000, 18(13):2515-2521.
- [10]McCulloch M, See C, Shu XJ, Broffman M, Kramer A, Fan WY, Gao J, Lieb W, Shieh K, Colford JM Jr: Astragalus-based chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials. J Clin Oncol 2006, 24(3):419-430.
- [11]Sen T, Dhara AK, Bhattacharjee S, Pal S, Nag chaudhuri AK: Antioxidant activity of the methanol fraction of pluchea indica root extract. Phytother Res 2002, 16(4):331-335.
- [12]Sen T, Nag chaudhuri AK: Antiinflammatory evaluation of a pluchea indica root extract. J Ethnopharmacol 1991, 33(1–2):135-141.
- [13]Gomes A, Saha A, Chatterjee I, Chakravarty AK: Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of pluchea indica less. (Asteraceae). Phytomedicine 2007, 14(9):637-643.
- [14]Sen T, Ghosh TK, Chaudhuri AK: Studies on the mechanism of anti-inflammatory and anti-ulcer activity of pluchea indica–probable involvement of 5-lipooxygenase pathway. Life Sci 1993, 52(8):737-743.
- [15]Mohamad S, Zin NM, Wahab HA, Ibrahim P, Sulaiman SF, Zahariluddin AS, Noor SS: Antituberculosis potential of some ethnobotanically selected malaysian plants. J Ethnopharmacol 2011, 133(3):1021-1026.
- [16]Li XK, Motwani M, Tong W, Bornmann W, Schwartz GK: Huanglian, a chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells. Mol Pharmacol 2000, 58(6):1287-1293.
- [17]Harborne JB: Phytochemical methods: a guide to modern techniques of plant analysis. 3rd edition. London, New York: Chapman and Hall; 1998.
- [18]Butler LG, Price ML, Brotherton JE: Vanillin assay for proanthocyanidins (condensed tannins): modification of the solvent for estimation of the degree of polymerization. J Agric Food Chem 1982, 49(3):1169-1174.
- [19]Janero DR: Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 1990, 9(6):515-540.
- [20]West KA, Zhang H, Brown MC, Nikolopoulos SN, Riedy MC, Horwitz AF, Turner CE: The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL). J Cell Biol 2001, 154(1):161-176.
- [21]Wink M, Ashour ML, El-Readi MZ: Secondary metabolites from plants inhibiting ABC transporters and reversing resistance of cancer cells and microbes to cytotoxic and antimicrobial agents. Front Microbiol 2012, 3:130.
- [22]Zamora-Ros R, Agudo A, Lujan-Barroso L, Romieu I, Ferrari P, Knaze V, Bueno-de-Mesquita HB, Leenders M, Travis RC, Navarro C, et al.: Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the european prospective investigation into cancer and nutrition (EPIC) study. Am J Clin Nutr 2012, 96(6):1398-1408.
- [23]Law PC, Auyeung KK, Chan LY, Ko JK: Astragalus saponins downregulate vascular endothelial growth factor under cobalt chloride-stimulated hypoxia in colon cancer cells. BMC Complement Altern Med 2012, 12:160. BioMed Central Full Text
- [24]Prasad R, Vaid M, Katiyar SK: Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway. PLoS One 2012, 7(8):e43064.
- [25]Ghavami G, Sardari S, Ali Shokrgozar M: Cheminformatics-based selection and synergism of herbal extracts with anticancer agents on drug resistance tumor cells-ACHN and A2780/CP cell lines. Comput Biol Med 2011, 41(8):665-674.
- [26]Tsai NM, Chen YL, Lee CC, Lin PC, Cheng YL, Chang WL, Lin SZ, Harn HJ: The natural compound n-butylidenephthalide derived from angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. J Neurochem 2006, 99(4):1251-1262.
- [27]Kumar AP, Bhaskaran S, Ganapathy M, Crosby K, Davis MD, Kochunov P, Schoolfield J, Yeh IT, Troyer DA, Ghosh R: Akt/cAMP-responsive element binding protein/cyclin D1 network: a novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate model mediated by nexrutine, a phellodendron amurense bark extract. Clin Cancer Res 2007, 13(9):2784-2794.
- [28]Vousden KH, Prives C: Blinded by the light: the growing complexity of p53. Cell 2009, 137(3):413-431.
- [29]Vogelstein B, Lane D, Levine AJ: Surfing the p53 network. Nature 2000, 408(6810):307-310.
- [30]Chen TP, Chen CM, Chang HW, Wang JS, Chang WC, Hsu SI, Cho CL: Increased expression of SKP2 and phospho-MAPK/ERK1/2 and decreased expression of p27 during tumor progression of cervical neoplasms. Gynecol Oncol 2007, 104(3):516-523.
- [31]Brady CA, Jiang D, Mello SS, Johnson TM, Jarvis LA, Kozak MM, Kenzelmann Broz D, Basak S, Park EJ, McLaughlin ME, et al.: Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 2011, 145(4):571-583.
- [32]Chen K, Albano A, Ho A, Keaney JF Jr: Activation of p53 by oxidative stress involves platelet-derived growth factor-beta receptor-mediated ataxia telangiectasia mutated (ATM) kinase activation. J Biol Chem 2003, 278(41):39527-39533.
- [33]Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT: ATM activation by oxidative stress. Science 2010, 330(6003):517-521.
- [34]Seoane J, Le HV, Massague J: Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature 2002, 419(6908):729-734.
- [35]Koz ST, Etem EO, Baydas G, Yuce H, Ozercan HI, Kuloglu T, Koz S, Etem A, Demir N: Effects of resveratrol on blood homocysteine level, on homocysteine induced oxidative stress, apoptosis and cognitive dysfunctions in rats. Brain Res 2012, 1484:29-38.
- [36]Bresgen N, Jaksch H, Lacher H, Ohlenschlager I, Uchida K, Eckl PM: Iron-mediated oxidative stress plays an essential role in ferritin-induced cell death. Free Radic Biol Med 2010, 48(10):1347-1357.
- [37]Feng Z, Hu W, Tang MS: Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci USA 2004, 101(23):8598-8602.
- [38]Lee YJ, Lee JH, Han HJ: Extracellular adenosine triphosphate protects oxidative stress-induced increase of p21(WAF1/Cip1) and p27(Kip1) expression in primary cultured renal proximal tubule cells: role of PI3K and Akt signaling. J Cell Physiol 2006, 209(3):802-810.
- [39]Bellacosa A, Kumar CC, Di Cristofano A, Testa JR: Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res 2005, 94:29-86.
- [40]Zhou BP, Hung MC: Novel targets of Akt, p21(cipl/WAF1), and MDM2. Semin Oncol 2002, 29(3 Suppl 11):62-70.
- [41]Testa JR, Bellacosa A: AKT plays a central role in tumorigenesis. Proc Natl Acad Sci USA 2001, 98(20):10983-10985.
- [42]Tsao AS, McDonnell T, Lam S, Putnam JB, Bekele N, Hong WK, Kurie JM: Increased phospho-AKT (Ser(473)) expression in bronchial dysplasia: implications for lung cancer prevention studies. Cancer Epidemiol Biomarkers Prev 2003, 12(7):660-664.
- [43]Balsara BR, Pei J, Mitsuuchi Y, Page R, Klein-Szanto A, Wang H, Unger M, Testa JR: Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions. Carcinogenesis 2004, 25(11):2053-2059.
- [44]Frida L, Rakotonirina S, Rakotonirina A, Savineau JP: In vivo and in vitro effects of bidens pilosa L. (Asteraceae) leaf aqueous and ethanol extracts on primed-oestrogenized rat uterine muscle. Afr J Tradit Complement Altern Med 2007, 5(1):79-91.