Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2014

Open Access 01-12-2014 | Research article

Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells

Authors: Amirah Abdul Rahman, A Rahman A Jamal, Roslan Harun, Norfilza Mohd Mokhtar, Wan Zurinah Wan Ngah

Published in: BMC Complementary Medicine and Therapies | Issue 1/2014

Login to get access

Abstract

Background

Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment.

Methods

In this study, we investigated the interaction of GTT and HC and its mode of cell death on glioma cell lines. GTT or HC alone and in combination were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) by [3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)- 2H- tetrazolium, inner salt] MTS assay. The interactions of each combination were evaluated by using the combination index (CI) obtained from an isobologram.

Results

Individually, GTT or HC displayed mild growth inhibitory effects against glioma cancer cell lines at concentration values ranging from 42–100 μg/ml and 75–119 μg/ml respectively. However, the combination of sub-lethal doses of GTT + HC dramatically enhanced the inhibition of glioma cancer cell proliferation and exhibited a strong synergistic effect on 1321N1 with CI of 0.55, and CI = 0.54 for SW1783. While in LN18 cells, moderate synergistic interaction of GTT + HC was observed with CI value of 0.73. Exposure of grade II, III and IV cells to combined treatments for 24 hours led to increased apoptosis as determined by annexin-V FITC/PI staining and caspase-3 apoptosis assay, showing caspase-3 activation of 27%, 7.1% and 79% respectively.

Conclusion

In conclusion, combined treatments with sub-effective doses of GTT and HC resulted in synergistic inhibition of cell proliferation through the induction of apoptosis of human glioma cells in vitro.
Appendix
Available only for authorised users
Literature
1.
go back to reference Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK: Malignant astrocytic glioma: genetics, biology, and paths to treatment. Gene Dev. 2007, 21 (21): 2683-2710. 10.1101/gad.1596707.CrossRefPubMed Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK: Malignant astrocytic glioma: genetics, biology, and paths to treatment. Gene Dev. 2007, 21 (21): 2683-2710. 10.1101/gad.1596707.CrossRefPubMed
2.
go back to reference Wrensch M, Rice T, Miike R, McMillan A, Lamborn KR, Aldape K, Prados MD: Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area. Neuro Oncol. 2006, 8 (1): 12-26. 10.1215/S1522851705000268.CrossRefPubMedPubMedCentral Wrensch M, Rice T, Miike R, McMillan A, Lamborn KR, Aldape K, Prados MD: Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area. Neuro Oncol. 2006, 8 (1): 12-26. 10.1215/S1522851705000268.CrossRefPubMedPubMedCentral
3.
go back to reference Miller CR, Perry A: Glioblastoma. Arch Pathol Lab Med. 2007, 131 (3): 397-406.PubMed Miller CR, Perry A: Glioblastoma. Arch Pathol Lab Med. 2007, 131 (3): 397-406.PubMed
4.
go back to reference Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009, 10 (5): 459-466. 10.1016/S1470-2045(09)70025-7.CrossRefPubMed Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009, 10 (5): 459-466. 10.1016/S1470-2045(09)70025-7.CrossRefPubMed
5.
go back to reference Wagner H, Ulrich-Merzenich G: Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009, 16 (2–3): 97-110.CrossRefPubMed Wagner H, Ulrich-Merzenich G: Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009, 16 (2–3): 97-110.CrossRefPubMed
6.
go back to reference Straetemans R, O'Brien T, Wouters L, Van Dun J, Janicot M, Bijnens L, Burzykowski T, Aerts M: Design and analysis of drug combination experiments. Biom J. 2005, 47 (3): 299-308. 10.1002/bimj.200410124.CrossRefPubMed Straetemans R, O'Brien T, Wouters L, Van Dun J, Janicot M, Bijnens L, Burzykowski T, Aerts M: Design and analysis of drug combination experiments. Biom J. 2005, 47 (3): 299-308. 10.1002/bimj.200410124.CrossRefPubMed
7.
go back to reference Viola V, Pilolli F, Piroddi M, Pierpaoli E, Orlando F, Provinciali M, Betti M, Mazzini F, Galli F: Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E. Gene Nutr. 2012, 7 (1): 29-41. 10.1007/s12263-011-0219-9.CrossRef Viola V, Pilolli F, Piroddi M, Pierpaoli E, Orlando F, Provinciali M, Betti M, Mazzini F, Galli F: Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E. Gene Nutr. 2012, 7 (1): 29-41. 10.1007/s12263-011-0219-9.CrossRef
8.
go back to reference Kannappan R, Gupta SC, Kim JH, Aggarwal BB: Tocotrienols fight cancer by targeting multiple cell signaling pathways. Gene Nutr. 2012, 7 (1): 43-52. 10.1007/s12263-011-0220-3.CrossRef Kannappan R, Gupta SC, Kim JH, Aggarwal BB: Tocotrienols fight cancer by targeting multiple cell signaling pathways. Gene Nutr. 2012, 7 (1): 43-52. 10.1007/s12263-011-0220-3.CrossRef
9.
go back to reference Patacsil D, Tran AT, Cho YS, Suy S, Saenz F, Malyukova I, Ressom H, Collins SP, Clarke R, Kumar D: Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells. J Nutr Biochem. 2012, 23 (1): 93-100. 10.1016/j.jnutbio.2010.11.012.CrossRefPubMed Patacsil D, Tran AT, Cho YS, Suy S, Saenz F, Malyukova I, Ressom H, Collins SP, Clarke R, Kumar D: Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells. J Nutr Biochem. 2012, 23 (1): 93-100. 10.1016/j.jnutbio.2010.11.012.CrossRefPubMed
10.
go back to reference Jeng JH, Wang YJ, Chang WH, Wu HL, Li CH, Uang BJ, Kang JJ, Lee JJ, Hahn LJ, Lin BR, Chang MC: Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells. Cell Mol Life Sci. 2004, 61 (1): 83-96. 10.1007/s00018-003-3272-8.CrossRefPubMed Jeng JH, Wang YJ, Chang WH, Wu HL, Li CH, Uang BJ, Kang JJ, Lee JJ, Hahn LJ, Lin BR, Chang MC: Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells. Cell Mol Life Sci. 2004, 61 (1): 83-96. 10.1007/s00018-003-3272-8.CrossRefPubMed
11.
go back to reference Pandey A, Bani S: Hydroxychavicol inhibits immune responses to mitigate cognitive dysfunction in rats. J Neuroimmunol. 2010, 226 (1–2): 48-58.CrossRefPubMed Pandey A, Bani S: Hydroxychavicol inhibits immune responses to mitigate cognitive dysfunction in rats. J Neuroimmunol. 2010, 226 (1–2): 48-58.CrossRefPubMed
12.
go back to reference Chakraborty JB, Mahato SK, Joshi K, Shinde V, Rakshit S, Biswas N, Choudhury Mukherjee I, Mandal L, Ganguly D, Chowdhury AA, Chaudhuri J, Paul K, Pal BC, Vinayagam J, Pal C, Manna A, Jaisankar P, Chaudhuri U, Konar A, Roy S, Bandyopadhyay S: Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance. Cancer Sci. 2012, 103 (1): 88-99. 10.1111/j.1349-7006.2011.02107.x.CrossRefPubMed Chakraborty JB, Mahato SK, Joshi K, Shinde V, Rakshit S, Biswas N, Choudhury Mukherjee I, Mandal L, Ganguly D, Chowdhury AA, Chaudhuri J, Paul K, Pal BC, Vinayagam J, Pal C, Manna A, Jaisankar P, Chaudhuri U, Konar A, Roy S, Bandyopadhyay S: Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance. Cancer Sci. 2012, 103 (1): 88-99. 10.1111/j.1349-7006.2011.02107.x.CrossRefPubMed
13.
go back to reference Sharma S, Khan IA, Ali I, Ali F, Kumar M, Kumar A, Johri RK, Abdullah ST, Bani S, Pandey A, Suri KA, Gupta BD, Satti NK, Dutt P, Qazi GN: Evaluation of the antimicrobial, antioxidant, and anti-inflammatory activities of hydroxychavicol for its potential use as an oral care agent. Antimicrob Agents Chemother. 2009, 53 (1): 216-222. 10.1128/AAC.00045-08.CrossRefPubMed Sharma S, Khan IA, Ali I, Ali F, Kumar M, Kumar A, Johri RK, Abdullah ST, Bani S, Pandey A, Suri KA, Gupta BD, Satti NK, Dutt P, Qazi GN: Evaluation of the antimicrobial, antioxidant, and anti-inflammatory activities of hydroxychavicol for its potential use as an oral care agent. Antimicrob Agents Chemother. 2009, 53 (1): 216-222. 10.1128/AAC.00045-08.CrossRefPubMed
14.
go back to reference Padma PR, Amonkar AJ, Bhide SV: Antimutagenic effects of betel leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines. Mutagenesis. 1989, 4 (2): 154-156. 10.1093/mutage/4.2.154.CrossRefPubMed Padma PR, Amonkar AJ, Bhide SV: Antimutagenic effects of betel leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines. Mutagenesis. 1989, 4 (2): 154-156. 10.1093/mutage/4.2.154.CrossRefPubMed
15.
go back to reference Ulrich-Merzenich G, Panek D, Zeitler H, Vetter H, Wagner H: Drug development from natural products: exploiting synergistic effects. Indian J Exp Biol. 2010, 48 (3): 208-219.PubMed Ulrich-Merzenich G, Panek D, Zeitler H, Vetter H, Wagner H: Drug development from natural products: exploiting synergistic effects. Indian J Exp Biol. 2010, 48 (3): 208-219.PubMed
16.
go back to reference Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006, 5 (10): 821-834. 10.1038/nrd2132.CrossRefPubMed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006, 5 (10): 821-834. 10.1038/nrd2132.CrossRefPubMed
17.
go back to reference Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984, 22: 27-55.CrossRefPubMed Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984, 22: 27-55.CrossRefPubMed
18.
go back to reference Zhao L, Wientjes MG, Au JL: Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses. Clin Cancer Res. 2004, 10 (23): 7994-8004. 10.1158/1078-0432.CCR-04-1087.CrossRefPubMed Zhao L, Wientjes MG, Au JL: Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses. Clin Cancer Res. 2004, 10 (23): 7994-8004. 10.1158/1078-0432.CCR-04-1087.CrossRefPubMed
19.
go back to reference Lamparska-Przybysz M, Gajkowska B, Motyl T: Cathepsins and BID are involved in the molecular switch between apoptosis and autophagy in breast cancer MCF-7 cells exposed to camptothecin. J Physiol Pharmacol. 2005, 56 (Suppl 3): 159-179.PubMed Lamparska-Przybysz M, Gajkowska B, Motyl T: Cathepsins and BID are involved in the molecular switch between apoptosis and autophagy in breast cancer MCF-7 cells exposed to camptothecin. J Physiol Pharmacol. 2005, 56 (Suppl 3): 159-179.PubMed
20.
go back to reference Collins MK, Lopez Rivas A: The control of apoptosis in mammalian cells. Trends Biochem Sci. 1993, 18 (8): 307-309. 10.1016/0968-0004(93)90042-L.CrossRefPubMed Collins MK, Lopez Rivas A: The control of apoptosis in mammalian cells. Trends Biochem Sci. 1993, 18 (8): 307-309. 10.1016/0968-0004(93)90042-L.CrossRefPubMed
21.
go back to reference Xu W, Du M, Zhao Y, Wang Q, Sun W, Chen B: gamma-Tocotrienol inhibits cell viability through suppression of beta-catenin/Tcf signaling in human colon carcinoma HT-29 cells. J Nutr Biochem. 2012, 23 (7): 800-807. 10.1016/j.jnutbio.2011.04.003.CrossRefPubMed Xu W, Du M, Zhao Y, Wang Q, Sun W, Chen B: gamma-Tocotrienol inhibits cell viability through suppression of beta-catenin/Tcf signaling in human colon carcinoma HT-29 cells. J Nutr Biochem. 2012, 23 (7): 800-807. 10.1016/j.jnutbio.2011.04.003.CrossRefPubMed
22.
go back to reference Campbell SE, Rudder B, Phillips RB, Whaley SG, Stimmel JB, Leesnitzer LM, Lightner J, Dessus-Babus S, Duffourc M, Stone WL, Menter DG, Newman RA, Yang P, Aggarwal BB, Krishnan K: gamma-Tocotrienol induces growth arrest through a novel pathway with TGFbeta2 in prostate cancer. Free Radic Biol Med. 2011, 50 (10): 1344-1354. 10.1016/j.freeradbiomed.2011.02.007.CrossRefPubMed Campbell SE, Rudder B, Phillips RB, Whaley SG, Stimmel JB, Leesnitzer LM, Lightner J, Dessus-Babus S, Duffourc M, Stone WL, Menter DG, Newman RA, Yang P, Aggarwal BB, Krishnan K: gamma-Tocotrienol induces growth arrest through a novel pathway with TGFbeta2 in prostate cancer. Free Radic Biol Med. 2011, 50 (10): 1344-1354. 10.1016/j.freeradbiomed.2011.02.007.CrossRefPubMed
23.
go back to reference Shah S, Gapor A, Sylvester PW: Role of caspase-8 activation in mediating vitamin E-induced apoptosis in murine mammary cancer cells. Nutr Cancer. 2003, 45 (2): 236-246. 10.1207/S15327914NC4502_14.CrossRefPubMed Shah S, Gapor A, Sylvester PW: Role of caspase-8 activation in mediating vitamin E-induced apoptosis in murine mammary cancer cells. Nutr Cancer. 2003, 45 (2): 236-246. 10.1207/S15327914NC4502_14.CrossRefPubMed
24.
go back to reference Shah S, Sylvester PW: Tocotrienol-induced caspase-8 activation is unrelated to death receptor apoptotic signaling in neoplastic mammary epithelial cells. Bull Exp Biol Med. 2004, 229 (8): 745-755. Shah S, Sylvester PW: Tocotrienol-induced caspase-8 activation is unrelated to death receptor apoptotic signaling in neoplastic mammary epithelial cells. Bull Exp Biol Med. 2004, 229 (8): 745-755.
25.
go back to reference Hemamalini MVDP V, Sivaramakrishnan S: Evaluation of the In vitro antioxidant, Anti-Enteropathogenic and Anticancer Efficacy of Natural and Synthetic Hydroxychavicol. Int J Med Res. 2012, 1 (5): 5- Hemamalini MVDP V, Sivaramakrishnan S: Evaluation of the In vitro antioxidant, Anti-Enteropathogenic and Anticancer Efficacy of Natural and Synthetic Hydroxychavicol. Int J Med Res. 2012, 1 (5): 5-
26.
go back to reference Kunysz EA, Michel AD, Whiting RL, Woods K: The human astrocytoma cell line 1321N1 contains M2-glandular type muscarinic receptors linked to phosphoinositide turnover. Br J Pharmacol. 1989, 96 (2): 271-278. 10.1111/j.1476-5381.1989.tb11813.x.CrossRefPubMedPubMedCentral Kunysz EA, Michel AD, Whiting RL, Woods K: The human astrocytoma cell line 1321N1 contains M2-glandular type muscarinic receptors linked to phosphoinositide turnover. Br J Pharmacol. 1989, 96 (2): 271-278. 10.1111/j.1476-5381.1989.tb11813.x.CrossRefPubMedPubMedCentral
27.
go back to reference Bárbara Meléndez AG-C, Yolanda R, Yolanda C-M, Angel R d L, Elisa P-M, Pilar M, Sofía T, Mar L, Guillermo V, Manuela M: Copy Number Alterations in Glioma Cell Lines. Glioma - Exploring Its Biology and Practical Relevance. Edited by: Ghosh DA. 2011, InTech: InTech, 429-448. Bárbara Meléndez AG-C, Yolanda R, Yolanda C-M, Angel R d L, Elisa P-M, Pilar M, Sofía T, Mar L, Guillermo V, Manuela M: Copy Number Alterations in Glioma Cell Lines. Glioma - Exploring Its Biology and Practical Relevance. Edited by: Ghosh DA. 2011, InTech: InTech, 429-448.
28.
go back to reference Diserens AC, de Tribolet N, Martin-Achard A, Gaide AC, Schnegg JF, Carrel S: Characterization of an established human malignant glioma cell line: LN-18. Acta Neuropathol. 1981, 53 (1): 21-28. 10.1007/BF00697180.CrossRefPubMed Diserens AC, de Tribolet N, Martin-Achard A, Gaide AC, Schnegg JF, Carrel S: Characterization of an established human malignant glioma cell line: LN-18. Acta Neuropathol. 1981, 53 (1): 21-28. 10.1007/BF00697180.CrossRefPubMed
29.
go back to reference Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC, Van Meir EG: Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 1999, 9 (3): 469-479. 10.1111/j.1750-3639.1999.tb00536.x.CrossRefPubMed Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC, Van Meir EG: Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 1999, 9 (3): 469-479. 10.1111/j.1750-3639.1999.tb00536.x.CrossRefPubMed
30.
go back to reference Flaman JM, Frebourg T, Moreau V, Charbonnier F, Martin C, Chappuis P, Sappino AP, Limacher IM, Bron L, Benhattar J: A simple p53 functional assay for screening cell lines, blood, and tumors. Proc Natl Acad Sci U S A. 1995, 92 (9): 3963-3967. 10.1073/pnas.92.9.3963.CrossRefPubMedPubMedCentral Flaman JM, Frebourg T, Moreau V, Charbonnier F, Martin C, Chappuis P, Sappino AP, Limacher IM, Bron L, Benhattar J: A simple p53 functional assay for screening cell lines, blood, and tumors. Proc Natl Acad Sci U S A. 1995, 92 (9): 3963-3967. 10.1073/pnas.92.9.3963.CrossRefPubMedPubMedCentral
31.
go back to reference Kok TM, Breda SG, Briede JJ: Genomics-based identification of molecular mechanisms behind the cancer preventive action of phytochemicals: potential and challenges. Curr Pharm Biotechnol. 2012, 13 (1): 255-264. 10.2174/138920112798868601.CrossRefPubMed Kok TM, Breda SG, Briede JJ: Genomics-based identification of molecular mechanisms behind the cancer preventive action of phytochemicals: potential and challenges. Curr Pharm Biotechnol. 2012, 13 (1): 255-264. 10.2174/138920112798868601.CrossRefPubMed
32.
go back to reference Arko L, Katsyv I, Park GE, Luan WP, Park JK: Experimental approaches for the treatment of malignant gliomas. Pharmacol Therapeut. 2010, 128 (1): 1-36. 10.1016/j.pharmthera.2010.04.015.CrossRef Arko L, Katsyv I, Park GE, Luan WP, Park JK: Experimental approaches for the treatment of malignant gliomas. Pharmacol Therapeut. 2010, 128 (1): 1-36. 10.1016/j.pharmthera.2010.04.015.CrossRef
33.
go back to reference Sylvester PW: Synergistic anticancer effects of combined gamma-tocotrienol with statin or receptor tyrosine kinase inhibitor treatment. Gene Nutr. 2012, 7 (1): 63-74. 10.1007/s12263-011-0225-y.CrossRef Sylvester PW: Synergistic anticancer effects of combined gamma-tocotrienol with statin or receptor tyrosine kinase inhibitor treatment. Gene Nutr. 2012, 7 (1): 63-74. 10.1007/s12263-011-0225-y.CrossRef
34.
go back to reference Shirode AB, Sylvester PW: Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling. Biomed Pharmacother. 2010, 64 (5): 327-332. 10.1016/j.biopha.2009.09.018.CrossRefPubMed Shirode AB, Sylvester PW: Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling. Biomed Pharmacother. 2010, 64 (5): 327-332. 10.1016/j.biopha.2009.09.018.CrossRefPubMed
35.
go back to reference de Bruin EC, Medema JP: Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev. 2008, 34 (8): 737-749. 10.1016/j.ctrv.2008.07.001.CrossRefPubMed de Bruin EC, Medema JP: Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev. 2008, 34 (8): 737-749. 10.1016/j.ctrv.2008.07.001.CrossRefPubMed
36.
go back to reference Raffray M, Cohen GM: Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death?. Pharmacol Ther. 1997, 75 (3): 153-177. 10.1016/S0163-7258(97)00037-5.CrossRefPubMed Raffray M, Cohen GM: Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death?. Pharmacol Ther. 1997, 75 (3): 153-177. 10.1016/S0163-7258(97)00037-5.CrossRefPubMed
37.
go back to reference Hsieh TC, Wu JM: Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin. Anticancer Res. 2009, 29 (10): 4025-4032.PubMedPubMedCentral Hsieh TC, Wu JM: Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin. Anticancer Res. 2009, 29 (10): 4025-4032.PubMedPubMedCentral
38.
go back to reference Zhang R, Banik NL, Ray SK: Combination of all-trans retinoic acid and interferon-gamma upregulated p27(kip1) and down regulated CDK2 to cause cell cycle arrest leading to differentiation and apoptosis in human glioblastoma LN18 (PTEN-proficient) and U87MG (PTEN-deficient) cells. Cancer Chemother Pharmacol. 2008, 62 (3): 407-416. 10.1007/s00280-007-0619-0.CrossRefPubMed Zhang R, Banik NL, Ray SK: Combination of all-trans retinoic acid and interferon-gamma upregulated p27(kip1) and down regulated CDK2 to cause cell cycle arrest leading to differentiation and apoptosis in human glioblastoma LN18 (PTEN-proficient) and U87MG (PTEN-deficient) cells. Cancer Chemother Pharmacol. 2008, 62 (3): 407-416. 10.1007/s00280-007-0619-0.CrossRefPubMed
39.
go back to reference Nakagawa Y, Suzuki T, Nakajima K, Ishii H, Ogata A: Biotransformation and cytotoxic effects of hydroxychavicol, an intermediate of safrole metabolism, in isolated rat hepatocytes. Chem Biol Interact. 2009, 180 (1): 89-97. 10.1016/j.cbi.2009.02.003.CrossRefPubMed Nakagawa Y, Suzuki T, Nakajima K, Ishii H, Ogata A: Biotransformation and cytotoxic effects of hydroxychavicol, an intermediate of safrole metabolism, in isolated rat hepatocytes. Chem Biol Interact. 2009, 180 (1): 89-97. 10.1016/j.cbi.2009.02.003.CrossRefPubMed
40.
go back to reference Chen CL, Chi CW, Liu TY: Enhanced hydroxychavicol-induced cytotoxic effects in glutathione-depleted HepG2 cells. Cancer Lett. 2000, 155 (1): 29-35. 10.1016/S0304-3835(00)00404-3.CrossRefPubMed Chen CL, Chi CW, Liu TY: Enhanced hydroxychavicol-induced cytotoxic effects in glutathione-depleted HepG2 cells. Cancer Lett. 2000, 155 (1): 29-35. 10.1016/S0304-3835(00)00404-3.CrossRefPubMed
41.
go back to reference Tan SW, Ramasamy R, Abdullah M, Vidyadaran S: Inhibitory effects of palm alpha-, gamma- and delta-tocotrienol on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Cell Immunol. 2011, 271 (2): 205-209. 10.1016/j.cellimm.2011.07.012.CrossRefPubMed Tan SW, Ramasamy R, Abdullah M, Vidyadaran S: Inhibitory effects of palm alpha-, gamma- and delta-tocotrienol on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Cell Immunol. 2011, 271 (2): 205-209. 10.1016/j.cellimm.2011.07.012.CrossRefPubMed
Metadata
Title
Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells
Authors
Amirah Abdul Rahman
A Rahman A Jamal
Roslan Harun
Norfilza Mohd Mokhtar
Wan Zurinah Wan Ngah
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2014
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-14-213

Other articles of this Issue 1/2014

BMC Complementary Medicine and Therapies 1/2014 Go to the issue