The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis

Investigational New Drugs

Volumn 28, Issue 4, 2010, Pages 392-401

  Kumar, G Harish ^a   Vidya Priyadarsini, R ^a   Vinothini, G ^a   Vidjaya Letchoumy, P ^a   Nagini, S ^a  

^a ANNAMALAI UNIVERSITY   (India)

Author keywords

Chemoprevention; DMBA; Hamster buccal pouch carcinogenesis; Neem

Indexed keywords

APOPTOTIC PROTEASE ACTIVATING FACTOR 1; AZADIRACHTIN; CASPASE 3; CASPASE 6; CASPASE 8; CASPASE 9; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLINE; CYTOCHROME C; FAS ANTIGEN; GLUTATHIONE TRANSFERASE; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIMONOID; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NIMBOLIDE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BID; PROTEIN P53; SURVIVIN; 7,12 DIMETHYLBENZ[A]ANTHRACENE; ANTINEOPLASTIC AGENT; CELL CYCLE PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; AZADIRACHTA INDICA; CANCER INCIDENCE; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CHEMOPROPHYLAXIS; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; IMMUNOHISTOCHEMISTRY; MALE; MOUTH CANCER; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; UPREGULATION; WESTERN BLOTTING; ANIMAL; CHEMICALLY INDUCED DISORDER; DISEASE MODEL; DRUG EFFECT; DRUG SCREENING; HAMSTER; METHODOLOGY; MOUTH TUMOR; RANDOMIZATION;

9,10-DIMETHYL-1,2-BENZANTHRACENE; ANIMALS; ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; AZADIRACHTA; CELL CYCLE PROTEINS; CELL PROLIFERATION; CRICETINAE; DISEASE MODELS, ANIMAL; DRUG SCREENING ASSAYS, ANTITUMOR; LIMONINS; MALE; MOUTH NEOPLASMS; RANDOM ALLOCATION;

EID: 77956630283     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-009-9263-3     Document Type: Article

References (42)

1. Khan N, Afaq F, Mukhtar H (2008) Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 10:475-510. doi:10.1089/ars.2007.1740
2. Sarkar FH (2007) LI YW: Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol Sin 28:1305-1315. doi:10.1111/j.1745-7254.2007.00689.x (Pubitemid 47366686)
3. Manson MM (2005) Inhibition of survival signaling by dietary polyphenols and indole-3-carbinol. Eur J Cancer 41:1842-1853. doi:10.1016/j.ejca.2005.05.008 (Pubitemid 41557672)
4. Visanji JM, Duthie SJ, Pirie L, Thompson DG, Padfield PJ (2004) Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase cell cycle arrest, DNA damage, and G2/M checkpoint activation. J Nutr 134:3121-3126
5. Karmakar S, Banik NL, Patel SJ, Ray SK (2007) Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells. Apoptosis 12:671-684. doi:10.1007/s10495-006-0024-x (Pubitemid 46411474)
6. Setzer WN, Setzer MC (2003) Plant-derived triterpenoids as potential antineoplastic agents. Mini Rev Med Chem 3:540-556. doi:10.2174/1389557033487854
7. Subapriya R, Nagini S (2005) Medicinal properties of neem leaves: a review. Curr Med Chem Anticancer Agents 5:149-156. doi:10.2174/1568011053174828 (Pubitemid 40347988)
8. Subapriya R, Nagini S (2005) Ethanolic neem leaf extract protects against N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in Wistar rats. Asian Pac J Cancer Prev 4:215-223
9. Subapriya R, Kumaraguruparan R, Nagini S (2006) Expression of PCNA, cytokeratin, Bcl-2 and p53 during chemoprevention of hamster buccal pouch carcinogenesis by ethanolic neem (Azadirachta indica) leaf extract. Clin Biochem 39:1080-1087. doi:10.1016/j.clinbiochem.2006.06.013 (Pubitemid 44737475)
10. Manikandan P, Vidjaya Letchoumy P, Gopalakrishnan M, Nagini S (2008) Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and in vivo modulation of biomarkers of chemoprevention in the hamster buccal pouch carcinogenesis model. Food Chem Toxicol 46:2332-2343. doi:10.1016/j. fct.2008.03.013
11. Koul A, Mukherjee N, Gangar SC (2006) Inhibitory effects of Azadirachta indica on DMBA-induced skin carcinogenesis in Balb/c mice. Mol Cell Biochem 283:47-55. doi:10.1007/s11010-006-2269-7
12. Bose A, Haque E, Baral R (2007) Neem leaf preparation induces apoptosis of tumour cells by releasing cytotoxic cytokines from human peripheral mononuclear cells. Phytother Res 21:914-920. doi:10.1002/ptr.2185 (Pubitemid 47582763)
13. Akudugu J, Gade G, Bohm L (2001) Cytotoxicity of azadirachtin A in human glioblastoma cell lines. Life Sci 68:1153-1160. doi:10.1016/S0024-3205 (00) 01017-1
14. Mordue AJ, Blackwell A (1993) Azadirachtin: an update. J Insect Physiol 39:903-924. doi:10.1016/0022-1910 (93) 90001-8
15. Cohen E, Quistad GB, Casida JE (1996) Cytotoxicity of nimbolide, epoxyazadiradione and other limonoids from neem insecticide. Life Sci 58:1075-1081. doi:10.1016/0024-3205 (96) 00061-6
16. Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, Isobe S, Tsushida T (2007) Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree (Azadirachta indica). Phytother Res 21:245-250. doi:10.1002/ptr.2058 (Pubitemid 46479675)
17. Harish Kumar G, Chandra Mohan K V P, Jagannadha Rao A, Nagini S (2009) Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells. Invest New Drugs 27:236-252. doi:10.1007/s10637-008-9170-z
18. Vidya Priyadarsini R, Manikandan P, Harish Kumar G, Nagini S (2009) The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobioticmetabolizing enzymes, DNA damage, antioxidants, invasion, and angiogenesis. Free Radic Res 43:492-504. doi:10.1080/10715760902870637
19. Shklar G (1999) Development of experimental oral carcinogenesis and its impact on current oral cancer research. J Dent Res 78:1768-1772. doi:10.1177/00220345990780120101
20. Fodstad O, Breistol K, Pettit GR, Shoemaker RH (1996) Boyd Mr: comparative antitumour activities of halichondrins and vinblastine against human tumor xenografts. J Exp Ther Oncol 1:119-125
21. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254. doi:10.1016/0003-2697 (76) 90527-3
22. Legrand-Poels S, Schoonbrodt S, Piette J (2000) Regulation of interleukin-6 gene expression by pro-inflammatory cytokines in a colon cancer cell line. Biochem J 349:765-773
23. Nagini S, Vidjaya Letchoumy P, Thangavelu A, Ramachandran CR (2009) Of humans and hamsters: A comparative evaluation of carcinogen activation, DNA damage, cell proliferation, apoptosis, invasion, and angiogenesis in oral cancer patients and hamster buccal pouch carcinomas. Oral Oncol (in press).
24. Kumar S, Suresh PK, Vijayababu MR (2006) Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3). J Ethnopharmacol 105:246-250. doi:10.1016/j.jep. 2005.11.006
25. Roy MK, Kobori M, Takenaka M (2006) Inhibition of colon cancer (HT-29) cell proliferation by a triterpenoid isolated from Azadirachta indica is accompanied by cell cycle arrest and upregulation of p21. Planta Med 72:917-923. doi:10.1055/s-2006-946694 (Pubitemid 44378955)
26. Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665-679. doi:10.1016/j. cell.2007.05.003
27. Maga G, Hubscher U (2003) Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 116:3051-3060. doi:10.1242/jcs.00653 (Pubitemid 37038954)
28. Haupt S, Berger M, Goldberg M (2003) Apoptosis-the p53 network. J Cell Sci 116:4077-4085. doi:10.1242/jcs.00739 (Pubitemid 37337082)
29. Sarkar FH, Li Y (2008) NF-kappaB: a potential target for cancer chemoprevention and therapy. Front Biosci 13:2950-2959. doi:10.2741/2900 (Pubitemid 351589211)
30. Van Waes C (2007) Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 13:1076-1082. doi:10.1158/1078-0432. CCR-06-2221
31. Karin M, Cao Y, Greten FR (2002) NF-kappa B in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301-310. doi:10.1038/nrc780
32. Wang W, Abbruzzese JL, Evans DB (1999) The nuclear factor kappa B RelA transcription factor is constititively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 5:119-127
33. Temme A, Rodriguez JA, Hendruschk S, Gunes S, Weigle B, Schakel K, Schmitz M, Bachmann M, Schackert G, Reiber EP (2007) Nuclear localization of survivin renders HeLa tumor cells more sensitive to apoptosis by induction of p53 and Bax. Cancer Lett 250:177-193. doi:10.1016/j.canlet.2006.09.020 (Pubitemid 46546648)
34. Shen Y, White E (2001) p53-dependent apoptosis pathways. Adv Cancer Res 82:55-84. doi:10.1016/S0065-230X (01) 82002-9
35. Di Ilio V, Pasquariello N, van der Esch AS (2006) Cytotoxic and antiproliferative effects induced by a nonterpenoid polar extract of A. indica seeds on 3T6 murine fibroblasts in culture. Mol Cell Biochem 287:69-77. doi:10.1007/s11010-005-9062-x (Pubitemid 44057394)
36. Sastry BS, Suresh Babu K, Hari Babu T, Chandrasekhar S, Srinivas PV, Saxena AK, Rao JM (2006) Synthesis and biological activity of amide derivatives of nimbolide. Bioorg Med Chem Lett 16:4391-4394. doi:10.1016/j.bmcl.2006.05.105 (Pubitemid 44018085)
37. Schlüter U (1987) Effects of azadirachtin on developing tissues of various insect larvae. In: Schmutterer H, Ascher KRS (eds) Natural pesticides from the neem tree and other tropical plants. Nairobi, Kenya, pp 331-348
38. Salehzadeh A, Akhkha A, Cushley W (2003) The antimitotic effect of the neem terpenoid azadirachtin on cultured insect cells. Insect Biochem Mol Biol 33:681-689. doi:10.1016/S0965-1748 (03) 00057-2
39. Anuradha A, Annadurai RS, Shashidhara LS (2007) Actin cytoskeleton as a putative target of the neem limonoid azadirachtin A. Insect Biochem Mol Biol 37:627-634. doi:10.1016/j. ibmb.2007.03.009
40. Singh SP, Abraham SK, Kesavan PC (1996) Radioprotection of mice following garlic pretreatment. Br J Cancer 74:102-104
41. Bhuvaneswari V, Velmurugan B, Nagini S (2004) Dose-dependent effect of tomato paste on 7, 12-dimethylbenz[a]anthraceneinduced hamster buccal pouch carcinogenesis. J Exp Clin Cancer Res 23:241-249 (Pubitemid 38943555)
42. Kigodi PG, Blasko G, Thebtaranonth Y (1989) Spectroscopic and biological investigation of nimbolide and 28-deoxonimbolide from Azadirachta indica. J Nat Prod 52:1246-1251. doi:10.1021/np50066a008