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Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines

Authors: Mohammad Faujul Kabir, Johari Mohd Ali, Mitra Abolmaesoomi, Onn Haji Hashim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts.

Method

Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition.

Result

Overall, MP-HX extract exhibited the highest antioxidant potential, with IC50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC50 = 57.81 ± 3.49 μg/mL) and HCT116 (IC50 = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC50 = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also demonstrated by their ability to induce caspase-dependent apoptotic cell death in all of the cancer cell lines tested. Cell cycle analysis suggested that both the MP-HX and MP-EA extracts were able to disrupt the cell cycle in most of the cancer cell lines.

Conclusions

MP-HX and MP-EA extracts demonstrated notable antioxidant, anti-proliferative, apoptosis induction and cancer cell cycle inhibition activities. These findings reflect the promising potentials of MP to be a source of novel phytochemical(s) with health promoting benefits that are also valuable for nutraceutical industry and cancer therapy.
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Literature
2.
go back to reference Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev. 2012;70(5):257–65.CrossRefPubMed Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev. 2012;70(5):257–65.CrossRefPubMed
3.
go back to reference Rukayah A. Tumbuhan liar berkhasiat ubatan, Cet. 1st ed. Kuala Lumpur: Dewan Bahasa dan Pustaka; 2006. Rukayah A. Tumbuhan liar berkhasiat ubatan, Cet. 1st ed. Kuala Lumpur: Dewan Bahasa dan Pustaka; 2006.
4.
go back to reference Perry LM, Metzger J. Medicinal plants of East and Southeast Asia: attributed properties and uses. Cambridge: MIT Press; 1980. Perry LM, Metzger J. Medicinal plants of East and Southeast Asia: attributed properties and uses. Cambridge: MIT Press; 1980.
5.
go back to reference Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, Ahmad S, Akira A, Israf D, Lajis N. Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals. J Biomed Biotechnol. 2010;2010:937642.CrossRefPubMed Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, Ahmad S, Akira A, Israf D, Lajis N. Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals. J Biomed Biotechnol. 2010;2010:937642.CrossRefPubMed
6.
go back to reference Mahadi M, Abdul Rahman N, Viswanathan D, Taib IS, Sulong A, Hakeem WA, Mohamad M, Khalid Mohammed I, Abidin IIZ, Rahman SA, et al. The potential effects of Melicope ptelefolia root extract as an anti-nociceptive and anti-inflammatory on animal models. Bull Fac Pharm Cairo Univ. 2016;54(2):237–41.CrossRef Mahadi M, Abdul Rahman N, Viswanathan D, Taib IS, Sulong A, Hakeem WA, Mohamad M, Khalid Mohammed I, Abidin IIZ, Rahman SA, et al. The potential effects of Melicope ptelefolia root extract as an anti-nociceptive and anti-inflammatory on animal models. Bull Fac Pharm Cairo Univ. 2016;54(2):237–41.CrossRef
7.
go back to reference Abas F, Shaari K, Israf DA, Syafri S, Zainal Z, Lajis NH. LC–DAD–ESI-MS analysis of nitric oxide inhibitory fractions of tenggek burung (Melicope ptelefolia Champ. ex Benth.). J Food Compos Anal. 2010;23(1):107–12.CrossRef Abas F, Shaari K, Israf DA, Syafri S, Zainal Z, Lajis NH. LC–DAD–ESI-MS analysis of nitric oxide inhibitory fractions of tenggek burung (Melicope ptelefolia Champ. ex Benth.). J Food Compos Anal. 2010;23(1):107–12.CrossRef
8.
go back to reference Shaari K, Suppaiah V, Wai LK, Stanslas J, Tejo BA, Israf DA, Abas F, Ismail IS, Shuaib NH, Zareen S, et al. Bioassay-guided identification of an anti-inflammatory prenylated acylphloroglucinol from Melicope ptelefolia and molecular insights into its interaction with 5-lipoxygenase. Bioorg Med Chem. 2011;19(21):6340–7.CrossRefPubMed Shaari K, Suppaiah V, Wai LK, Stanslas J, Tejo BA, Israf DA, Abas F, Ismail IS, Shuaib NH, Zareen S, et al. Bioassay-guided identification of an anti-inflammatory prenylated acylphloroglucinol from Melicope ptelefolia and molecular insights into its interaction with 5-lipoxygenase. Bioorg Med Chem. 2011;19(21):6340–7.CrossRefPubMed
9.
go back to reference Xu JF, Zhao HJ, Wang XB, Li ZR, Luo J, Yang MH, Yang L, Yu WY, Yao HQ, Luo JG, et al. (+/−)-Melicolones A and B, rearranged prenylated acetophenone stereoisomers with an unusual 9-oxatricyclo[3.2.1.1(3, 8)]nonane core from the leaves of Melicope ptelefolia. Org Lett. 2015;17(1):146–9.CrossRefPubMed Xu JF, Zhao HJ, Wang XB, Li ZR, Luo J, Yang MH, Yang L, Yu WY, Yao HQ, Luo JG, et al. (+/−)-Melicolones A and B, rearranged prenylated acetophenone stereoisomers with an unusual 9-oxatricyclo[3.2.1.1(3, 8)]nonane core from the leaves of Melicope ptelefolia. Org Lett. 2015;17(1):146–9.CrossRefPubMed
10.
go back to reference Singleton VL, Rossi JA. Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents. Am J Enol Vitic. 1965;16:144–58. Singleton VL, Rossi JA. Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents. Am J Enol Vitic. 1965;16:144–58.
11.
go back to reference Chang C-C, Yang M-H, Wen H-M, Chern J-C. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal. 2002;10(3):178–82. Chang C-C, Yang M-H, Wen H-M, Chern J-C. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal. 2002;10(3):178–82.
12.
go back to reference Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal Biochem. 1996;239:70–6.CrossRefPubMed Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal Biochem. 1996;239:70–6.CrossRefPubMed
13.
go back to reference Re R, Pellegrini N, Proteggente A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26:1231–7.CrossRefPubMed Re R, Pellegrini N, Proteggente A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26:1231–7.CrossRefPubMed
14.
go back to reference Sharma OP, Bhat TK. DPPH antioxidant assay revisited. Food Chem. 2009;113(4):1202–5.CrossRef Sharma OP, Bhat TK. DPPH antioxidant assay revisited. Food Chem. 2009;113(4):1202–5.CrossRef
15.
go back to reference Wolfe KL, Liu RH. Cellular antioxidant assay for assessing antioxidants, foods, and dietary supplements. J Agric Food Chem. 2007;55(22):8896–907.CrossRefPubMed Wolfe KL, Liu RH. Cellular antioxidant assay for assessing antioxidants, foods, and dietary supplements. J Agric Food Chem. 2007;55(22):8896–907.CrossRefPubMed
16.
go back to reference Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313–52.CrossRefPubMed Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313–52.CrossRefPubMed
17.
go back to reference Pereira DM, Valentão P, Pereira JA, Andrade PB. Phenolics: From Chemistry to Biology. Molecules. 2009;14(6):2202–11.CrossRef Pereira DM, Valentão P, Pereira JA, Andrade PB. Phenolics: From Chemistry to Biology. Molecules. 2009;14(6):2202–11.CrossRef
18.
go back to reference Abbas M, Saeed F, Anjum FM, Afzaal M, Tufail T, Bashir MS, Ishtiaq A, Hussain S, Suleria HAR. Natural polyphenols: An overview. Int J Food Prop. 2016:1–11. Abbas M, Saeed F, Anjum FM, Afzaal M, Tufail T, Bashir MS, Ishtiaq A, Hussain S, Suleria HAR. Natural polyphenols: An overview. Int J Food Prop. 2016:1–11.
19.
go back to reference Tapas A, Sakarkar D, Kakde R. Flavonoids as nutraceuticals: A review. Trop J Pharm Res. 2008;7(3):1089–99.CrossRef Tapas A, Sakarkar D, Kakde R. Flavonoids as nutraceuticals: A review. Trop J Pharm Res. 2008;7(3):1089–99.CrossRef
20.
go back to reference Cheng Z, Moore J, Yu L. High-throughput relative DPPH radical scavenging capacity assay. J Agric Food Chem. 2006;54(20):7429–36.CrossRefPubMed Cheng Z, Moore J, Yu L. High-throughput relative DPPH radical scavenging capacity assay. J Agric Food Chem. 2006;54(20):7429–36.CrossRefPubMed
21.
go back to reference Liu RH, Finley J. Potential cell culture models for antioxidant research. J Agric Food Chem. 2005;53(10):4311–4.CrossRefPubMed Liu RH, Finley J. Potential cell culture models for antioxidant research. J Agric Food Chem. 2005;53(10):4311–4.CrossRefPubMed
22.
go back to reference Song W, Derito CM, Liu MK, He X, Dong M, Liu RH. Cellular antioxidant activity of common vegetables. J Agric Food Chem. 2010;58(11):6621–9.CrossRefPubMed Song W, Derito CM, Liu MK, He X, Dong M, Liu RH. Cellular antioxidant activity of common vegetables. J Agric Food Chem. 2010;58(11):6621–9.CrossRefPubMed
23.
go back to reference Imeh U, Khokhar S. Distribution of conjugated and free phenols in fruits: antioxidant activity and cultivar variations. J Agric Food Chem. 2002;50(22):6301–6.CrossRefPubMed Imeh U, Khokhar S. Distribution of conjugated and free phenols in fruits: antioxidant activity and cultivar variations. J Agric Food Chem. 2002;50(22):6301–6.CrossRefPubMed
24.
go back to reference Van Engeland M, Nieland LJW, Ramaekers FCS, Schutte B, Reutelingsperger CPM. Annexin V-affinity assay: A review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 1998;31:1–9.CrossRefPubMed Van Engeland M, Nieland LJW, Ramaekers FCS, Schutte B, Reutelingsperger CPM. Annexin V-affinity assay: A review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 1998;31:1–9.CrossRefPubMed
25.
go back to reference Richardson JS, Sethi G, Lee GS, Malek SN. Chalepin: isolated from Ruta angustifolia L. Pers induces mitochondrial mediated apoptosis in lung carcinoma cells. BMC Complement Altern Med. 2016;16(1):389.CrossRefPubMedPubMedCentral Richardson JS, Sethi G, Lee GS, Malek SN. Chalepin: isolated from Ruta angustifolia L. Pers induces mitochondrial mediated apoptosis in lung carcinoma cells. BMC Complement Altern Med. 2016;16(1):389.CrossRefPubMedPubMedCentral
27.
go back to reference Bai L, Wang S. Targeting apoptosis pathways for new cancer therapeutics. Annu Rev Med. 2014;65:139–55.CrossRefPubMed Bai L, Wang S. Targeting apoptosis pathways for new cancer therapeutics. Annu Rev Med. 2014;65:139–55.CrossRefPubMed
29.
go back to reference Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 2004;5(11):897–907.CrossRefPubMed Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 2004;5(11):897–907.CrossRefPubMed
30.
go back to reference Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36:131–49.CrossRefPubMed Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36:131–49.CrossRefPubMed
32.
go back to reference Lee YZ, Shaari K, Cheema MS, Tham CL, Sulaiman MR, Israf DA. An orally active geranyl acetophenone attenuates airway remodeling in a murine model of chronic asthma. Eur J Pharmacol. 2017;797:53–64.CrossRefPubMed Lee YZ, Shaari K, Cheema MS, Tham CL, Sulaiman MR, Israf DA. An orally active geranyl acetophenone attenuates airway remodeling in a murine model of chronic asthma. Eur J Pharmacol. 2017;797:53–64.CrossRefPubMed
33.
go back to reference Tan JW, Israf DA, Harith HH, Md Hashim NF, Ng CH, Shaari K, Tham CL. Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis. Toxicol Appl Pharmacol. 2017;319:47–58.CrossRefPubMed Tan JW, Israf DA, Harith HH, Md Hashim NF, Ng CH, Shaari K, Tham CL. Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis. Toxicol Appl Pharmacol. 2017;319:47–58.CrossRefPubMed
34.
go back to reference Chong YJ, Musa NF, Ng CH, Shaari K, Israf DA, Tham CL. Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells. J Ethnopharmacol. 2016;192:248–55.CrossRefPubMed Chong YJ, Musa NF, Ng CH, Shaari K, Israf DA, Tham CL. Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells. J Ethnopharmacol. 2016;192:248–55.CrossRefPubMed
35.
go back to reference Shaari K, Zareen S, Akhtar MN, Lajis NH. Chemical constituents of Melicope ptelefolia. Nat Prod Commun. 2011;6(3):343–8.PubMed Shaari K, Zareen S, Akhtar MN, Lajis NH. Chemical constituents of Melicope ptelefolia. Nat Prod Commun. 2011;6(3):343–8.PubMed
36.
go back to reference Tiwari BK, Brunton N, Brennan CS. Handbook of plant food phytochemicals: sources, stability and extraction. Hoboken N.J: Wiley-Blackwell; 2012. Tiwari BK, Brunton N, Brennan CS. Handbook of plant food phytochemicals: sources, stability and extraction. Hoboken N.J: Wiley-Blackwell; 2012.
37.
go back to reference Yan SL, Huang CY, Wu ST, Yin MC. Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines. Toxicol In Vitro. 2010;24(3):842–8.CrossRefPubMed Yan SL, Huang CY, Wu ST, Yin MC. Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines. Toxicol In Vitro. 2010;24(3):842–8.CrossRefPubMed
38.
go back to reference Liu Y, Bi T, Wang G, Dai W, Wu G, Qian L, Gao Q, Shen G. Lupeol inhibits proliferation and induces apoptosis of human pancreatic cancer PCNA-1 cells through AKT/ERK pathways. Naunyn Schmiedeberg's Arch Pharmacol. 2015;388(3):295–304.CrossRef Liu Y, Bi T, Wang G, Dai W, Wu G, Qian L, Gao Q, Shen G. Lupeol inhibits proliferation and induces apoptosis of human pancreatic cancer PCNA-1 cells through AKT/ERK pathways. Naunyn Schmiedeberg's Arch Pharmacol. 2015;388(3):295–304.CrossRef
39.
go back to reference Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem. 2002;50(25):7449–54.CrossRefPubMed Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem. 2002;50(25):7449–54.CrossRefPubMed
40.
go back to reference Shoaib M, Shah SW, Ali N, Shah I, Ullah S, Ghias M, Tahir MN, Gul F, Akhtar S, Ullah A, et al. Scientific investigation of crude alkaloids from medicinal plants for the management of pain. BMC Complement Altern Med. 2016;16:178.CrossRefPubMedPubMedCentral Shoaib M, Shah SW, Ali N, Shah I, Ullah S, Ghias M, Tahir MN, Gul F, Akhtar S, Ullah A, et al. Scientific investigation of crude alkaloids from medicinal plants for the management of pain. BMC Complement Altern Med. 2016;16:178.CrossRefPubMedPubMedCentral
41.
go back to reference Low M, Khoo CS, Munch G, Govindaraghavan S, Sucher NJ. An in vitro study of anti-inflammatory activity of standardised Andrographis paniculata extracts and pure andrographolide. BMC Complement Altern Med. 2015;15:18.CrossRefPubMedPubMedCentral Low M, Khoo CS, Munch G, Govindaraghavan S, Sucher NJ. An in vitro study of anti-inflammatory activity of standardised Andrographis paniculata extracts and pure andrographolide. BMC Complement Altern Med. 2015;15:18.CrossRefPubMedPubMedCentral
Metadata
Title
Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines
Authors
Mohammad Faujul Kabir
Johari Mohd Ali
Mitra Abolmaesoomi
Onn Haji Hashim
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1761-9

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