Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231

Authors: Muhammad Luqman Nordin, Arifah Abdul Kadir, Zainul Amiruddin Zakaria, Rasedee Abdullah, Muhammad Nazrul Hakim Abdullah

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

Login to get access

Abstract

Background

Ardisia crispa Thunb. D.C is used mostly in some parts of the Asian region by traditional practitioners to treat certain diseases associated with oxidative stress and inflammation including cancer and rheumatism. In Malaysia, it is popularly known as ‘Mata Ayam’ and local traditional practitioners believed that the root of the plant is therapeutically beneficial.

Methods

The cytotoxic effect of hydromethanolic extract of A. crispa and its solvents partitions (ethyl acetate and aqueous extracts) against breast cancer cells were evaluated by using MTT assay. The cells were treated with concentration of extracts ranging from 15.63 μg/mL- 1000 μg/mL for 72 h. The quantification of phenolic and flavonoid contents of the extracts were carried out to determine the relationship between of phytochemical compounds responsible for cytotoxic and antioxidative activities. The antioxidant capacity was measured by DPPH and ABTS free radical scavenging assay and expressed as milligram (mg) Trolox equivalent antioxidant capacity per 1 g (g) of tested extract.

Results

The hydromethanolic and ethyl acetate extracts showed moderate cytotoxic effect against MCF-7 with IC50 values of 57.35 ± 19.33 μg/mL, and 54.98 ± 14.10 μg/mL, respectively but aqueous extract was inactive against MCF-7. For MDA-MB-231, hydromethanolic, ethyl acetate and aqueous extracts exhibited weak cytotoxic effects against MDA-MB-231 with IC50 values more than 100 μg/mL. The plant revealed high total phenolic content, total flavonoid and antioxidant capacity.

Conclusion

The response of different type of breast cancer cell lines towards A. crispa extract and its partitions varied. Accordingly, hydromethanolic and ethyl acetate extracts appear to be more cytotoxic to oestrogen receptor (ER) positive breast cancer than oestrogen receptor (ER) negative breast cancer. However, aqueous extract appears to have poor activity to both types of breast cancer. Besides that, hydromethanolic and ethyl acetate extracts exhibit higher TPC, TFC and antioxidant capacity compared to aqueous extract. Synergistic effect of anticancer and antioxidant bioactives compounds of A. crispa plausibly contributed to the cytotoxic effects of the extract.
Literature
1.
go back to reference Rutterman GR, Winthrow SJ, Mac Ewen EG. Tumors of the mammary gland. In: Winthrow SJ, Mac Ewen EG, Saunders Co WB, editors. Small Animal Clinical Oncology. 3rd ed. Philadelphia; 2000. p. 450–67. Rutterman GR, Winthrow SJ, Mac Ewen EG. Tumors of the mammary gland. In: Winthrow SJ, Mac Ewen EG, Saunders Co WB, editors. Small Animal Clinical Oncology. 3rd ed. Philadelphia; 2000. p. 450–67.
2.
go back to reference Ly D, Forman D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence rates. Int J Cancer. 2013;132(8):1918–26.CrossRefPubMed Ly D, Forman D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence rates. Int J Cancer. 2013;132(8):1918–26.CrossRefPubMed
3.
4.
go back to reference Lakhani S, Ellis I, Schnitt S, et al. WHO classification of Tumours of the breast. 4th ed. Lyon: IARC Press; 2012. Lakhani S, Ellis I, Schnitt S, et al. WHO classification of Tumours of the breast. 4th ed. Lyon: IARC Press; 2012.
5.
go back to reference Vuong D, Simpson PT, Green B, Cummings MC, Lakhani SR. Molecular classification of breast cancer. Virchows Arch. 2014;465(1):1–14.CrossRefPubMed Vuong D, Simpson PT, Green B, Cummings MC, Lakhani SR. Molecular classification of breast cancer. Virchows Arch. 2014;465(1):1–14.CrossRefPubMed
6.
go back to reference Viale G. The current state of breast cancer classification. Ann Oncol. 2012;23(suppl 10):x207–10.CrossRefPubMed Viale G. The current state of breast cancer classification. Ann Oncol. 2012;23(suppl 10):x207–10.CrossRefPubMed
7.
go back to reference Pinder SE, Ellis IO, Galea M, O'rouke S, Blamey RW, Elston CW. Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology. 1994;24(1):41–7.CrossRefPubMed Pinder SE, Ellis IO, Galea M, O'rouke S, Blamey RW, Elston CW. Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology. 1994;24(1):41–7.CrossRefPubMed
8.
go back to reference Joseph RB. Encyclopedia of cancer : volume 1 A-R. New York: Academic Press; 2002. Joseph RB. Encyclopedia of cancer : volume 1 A-R. New York: Academic Press; 2002.
10.
go back to reference Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME, Collins-Burow BM. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res. 2012;14(3):R79.CrossRefPubMedPubMedCentral Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME, Collins-Burow BM. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res. 2012;14(3):R79.CrossRefPubMedPubMedCentral
11.
go back to reference Hamsin DEZA, Hamid RA, Yazan LS, Taib CNM, Ting YL. The hexane fraction of Ardisia crispa Thunb. A. DC. Roots inhibits inflammation-induced angiogenesis. BMC Complement Altern Med. 2013;13(1):1.CrossRef Hamsin DEZA, Hamid RA, Yazan LS, Taib CNM, Ting YL. The hexane fraction of Ardisia crispa Thunb. A. DC. Roots inhibits inflammation-induced angiogenesis. BMC Complement Altern Med. 2013;13(1):1.CrossRef
12.
go back to reference Nordin ML, Abdul Kadir A, Zakaria ZA, Othman F, Abdullah R, Abdullah MNH. Cytotoxicity and apoptosis induction of Ardisia crispa and its solvent partitions against Mus musculus mammary carcinoma cell line (4T1). Evid Based Complement Alternat Med. 2017;2017 Nordin ML, Abdul Kadir A, Zakaria ZA, Othman F, Abdullah R, Abdullah MNH. Cytotoxicity and apoptosis induction of Ardisia crispa and its solvent partitions against Mus musculus mammary carcinoma cell line (4T1). Evid Based Complement Alternat Med. 2017;2017
13.
go back to reference Roslida, AH, Kim, KH. (2008). PHCOG MAG.: Research Article Anti-inflammatory and anti-hyperalgesic effects of Ardisia crispa Thunb. DC. Roslida, AH, Kim, KH. (2008). PHCOG MAG.: Research Article Anti-inflammatory and anti-hyperalgesic effects of Ardisia crispa Thunb. DC.
14.
go back to reference Christophe W. Medicinal plants of Southeast Asia. Selangor: Prentice Hall; 2002. Christophe W. Medicinal plants of Southeast Asia. Selangor: Prentice Hall; 2002.
15.
go back to reference Roslida AH, Teh YH, Kim KH. Evaluation of anti-ulcer activity of Ardisia crispa Thunb. DC Pharmacognosy Res. 2009;1(5):250. Roslida AH, Teh YH, Kim KH. Evaluation of anti-ulcer activity of Ardisia crispa Thunb. DC Pharmacognosy Res. 2009;1(5):250.
16.
go back to reference Kang YH, Kim WH, Park MK, Han BH. Antimetastatic and antitumor effects of benzoquinonoid AC7-1 from Ardisia crispa. Int J Cancer. 2001;93(5):736–40.CrossRefPubMed Kang YH, Kim WH, Park MK, Han BH. Antimetastatic and antitumor effects of benzoquinonoid AC7-1 from Ardisia crispa. Int J Cancer. 2001;93(5):736–40.CrossRefPubMed
17.
go back to reference Roslida AH, Fezah O, Yeong LT. Suppression of DMBA/croton oil-induced mouse skin tumor promotion by Ardisia crispa root hexane extract. Asian Pac J Cancer Prev. 2011;12(3):665–9.PubMed Roslida AH, Fezah O, Yeong LT. Suppression of DMBA/croton oil-induced mouse skin tumor promotion by Ardisia crispa root hexane extract. Asian Pac J Cancer Prev. 2011;12(3):665–9.PubMed
18.
go back to reference Sowndhararajan K, Kang SC. Protective effect of ethyl acetate fraction of Acacia ferruginea DC. Against ethanol-induced gastric ulcer in rats. J Ethopharmacology. 2013;148:175–81.CrossRef Sowndhararajan K, Kang SC. Protective effect of ethyl acetate fraction of Acacia ferruginea DC. Against ethanol-induced gastric ulcer in rats. J Ethopharmacology. 2013;148:175–81.CrossRef
19.
go back to reference Achenef B, Arifah K. Cytotoxic effects of conjugated linoleic acids on human breast cancer cells (MCF7). Cancer Res. 2012;5(1):11–6. Achenef B, Arifah K. Cytotoxic effects of conjugated linoleic acids on human breast cancer cells (MCF7). Cancer Res. 2012;5(1):11–6.
20.
go back to reference Ayob Z, Mohd Bohari SP, Abd Samad A, Jamil S. Cytotoxic activities against breast cancer cells of local Justicia gendarussa crude extracts. Evid Based Complement Alternat Med. 2014;2014 Ayob Z, Mohd Bohari SP, Abd Samad A, Jamil S. Cytotoxic activities against breast cancer cells of local Justicia gendarussa crude extracts. Evid Based Complement Alternat Med. 2014;2014
21.
go back to reference Tantengco OAG, Jacinto SD. Cytotoxic activity of crude extracts and fractions from Premna odorata (Blanco), Artocarpus camansi (Blanco) and Gliricidia sepium (Jacq.) against selected human cancer cell lines. Asian Pacific J Tropical Biomedicine. 2015;5(12):1037–41.CrossRef Tantengco OAG, Jacinto SD. Cytotoxic activity of crude extracts and fractions from Premna odorata (Blanco), Artocarpus camansi (Blanco) and Gliricidia sepium (Jacq.) against selected human cancer cell lines. Asian Pacific J Tropical Biomedicine. 2015;5(12):1037–41.CrossRef
22.
go back to reference Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005;11:127–52.CrossRefPubMed Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005;11:127–52.CrossRefPubMed
23.
go back to reference Baharum Z, Akim AM, Taufiq-Yap YH, Hamid RA, Kasran R. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao. Molecules. 2014;19(11):18317–31.CrossRefPubMed Baharum Z, Akim AM, Taufiq-Yap YH, Hamid RA, Kasran R. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao. Molecules. 2014;19(11):18317–31.CrossRefPubMed
24.
go back to reference Vijayarathna S, Sasidharan S. Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines. Asian Pacific J Tropical Biomedicine. 2012;2(10):826–9.CrossRef Vijayarathna S, Sasidharan S. Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines. Asian Pacific J Tropical Biomedicine. 2012;2(10):826–9.CrossRef
25.
go back to reference Iqbal S, Younas U, Chan KW, Sarfraz RA, Uddin MK. Proximatecomposition and antioxidant potential of leaves from three varieties of mulberry (Morus sp.): a comparative study. Int J Mol Sci. 2012;13(6):6651–64.CrossRefPubMedPubMedCentral Iqbal S, Younas U, Chan KW, Sarfraz RA, Uddin MK. Proximatecomposition and antioxidant potential of leaves from three varieties of mulberry (Morus sp.): a comparative study. Int J Mol Sci. 2012;13(6):6651–64.CrossRefPubMedPubMedCentral
26.
go back to reference Chan KW, Iqbal S, Khong NM, Babji AS. Preparation of deodorized antioxidant rich extracts from 15 selected spices through optimized aqueous extraction. J Med Plants Res. 2011;5:6067–75. Chan KW, Iqbal S, Khong NM, Babji AS. Preparation of deodorized antioxidant rich extracts from 15 selected spices through optimized aqueous extraction. J Med Plants Res. 2011;5:6067–75.
27.
go back to reference Chan KW, Iqbal S, Khong NM, Ooi DJ, Ismail M. Antioxidant activityof phenolics–saponins rich fraction prepared from defatted kenaf seed meal. LWT-Food Science and Technology. 2014;56(1):181–6.CrossRef Chan KW, Iqbal S, Khong NM, Ooi DJ, Ismail M. Antioxidant activityof phenolics–saponins rich fraction prepared from defatted kenaf seed meal. LWT-Food Science and Technology. 2014;56(1):181–6.CrossRef
28.
go back to reference Yahya F, Mamat SS, Kamarolzaman MFF, Seyedan AA, Jakius KF, Mahmood ND, Shahril MS, Suhaili Z, Mohtarrudin N, Susanti D, Somchit MN. Hepatoprotective activity of methanolic extract of Bauhinia purpurea leaves against paracetamol-induced hepatic damage in rats. Evid Based Complement Alternat Med. 2013; Yahya F, Mamat SS, Kamarolzaman MFF, Seyedan AA, Jakius KF, Mahmood ND, Shahril MS, Suhaili Z, Mohtarrudin N, Susanti D, Somchit MN. Hepatoprotective activity of methanolic extract of Bauhinia purpurea leaves against paracetamol-induced hepatic damage in rats. Evid Based Complement Alternat Med. 2013;
29.
go back to reference Atjanasuppat K, Wongkham W, Meepowpan P, Kittakoop P, Sobhon P, Bartlett A, Whitfield PJ. In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand. J Ethnopharmacol. 2009;123(3):475–82.CrossRefPubMed Atjanasuppat K, Wongkham W, Meepowpan P, Kittakoop P, Sobhon P, Bartlett A, Whitfield PJ. In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand. J Ethnopharmacol. 2009;123(3):475–82.CrossRefPubMed
30.
go back to reference Boik J. Natural compounds in cancer therapy. Minnesota: Oregon Medical Press; 2001. Boik J. Natural compounds in cancer therapy. Minnesota: Oregon Medical Press; 2001.
31.
go back to reference Lee CC, Houghton P. Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer. J Ethnopharmacol. 2005;100(3):237–43.CrossRefPubMed Lee CC, Houghton P. Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer. J Ethnopharmacol. 2005;100(3):237–43.CrossRefPubMed
32.
go back to reference Alsemari A, Alkhodairy F, Aldakan A, Al-Mohanna M, Bahoush E, Shinwari Z, Alaiya A. The selective cytotoxic anti-cancer properties and proteomic analysis of Trigonella Foenum-Graecum. BMC Complement Altern Med. 2014;14(1):1.CrossRef Alsemari A, Alkhodairy F, Aldakan A, Al-Mohanna M, Bahoush E, Shinwari Z, Alaiya A. The selective cytotoxic anti-cancer properties and proteomic analysis of Trigonella Foenum-Graecum. BMC Complement Altern Med. 2014;14(1):1.CrossRef
33.
go back to reference Al-Barazanjy RK, Dizaye K, Al-Asadye A. Cytotoxic and cytogenetic effects of Salvia officinalis on different tumor cell lines. Middle East J Int Med`. 2013;6(4):15–25.CrossRef Al-Barazanjy RK, Dizaye K, Al-Asadye A. Cytotoxic and cytogenetic effects of Salvia officinalis on different tumor cell lines. Middle East J Int Med`. 2013;6(4):15–25.CrossRef
34.
go back to reference Phang CW, Malek SNA, Ibrahim H, Wahab NA. Antioxidant properties of crude and fractionated extracts of Alpinia mutica rhizomes and their total phenolic content. Afr J Pharm Pharmacol. 2011;5(7):842–52. Phang CW, Malek SNA, Ibrahim H, Wahab NA. Antioxidant properties of crude and fractionated extracts of Alpinia mutica rhizomes and their total phenolic content. Afr J Pharm Pharmacol. 2011;5(7):842–52.
35.
go back to reference Mau JL, Chang CN, Huang SJ, Chen CC. Antioxidant properties of methanolic extracts from Grifola frondosa, Morchella esculenta and Termitomyces albuminosus mycelia. Food Chem. 2004;87(1):111–8.CrossRef Mau JL, Chang CN, Huang SJ, Chen CC. Antioxidant properties of methanolic extracts from Grifola frondosa, Morchella esculenta and Termitomyces albuminosus mycelia. Food Chem. 2004;87(1):111–8.CrossRef
36.
go back to reference Saeed N, Khan MR, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med. 2012;12(1):1.CrossRef Saeed N, Khan MR, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med. 2012;12(1):1.CrossRef
37.
go back to reference Zhao HX, Zhang HS, Yang SF. Phenolic compounds and its antioxidant activities in ethanolic extracts from seven cultivars of Chinese jujube. Food Sci Human Wellness. 2014;3(3):183–90.CrossRef Zhao HX, Zhang HS, Yang SF. Phenolic compounds and its antioxidant activities in ethanolic extracts from seven cultivars of Chinese jujube. Food Sci Human Wellness. 2014;3(3):183–90.CrossRef
38.
go back to reference Baba SA, Malik SA. Determination of total phenolic and flavonoid content, antimicrobial and antioxidant activity of a root extract of Arisaema jacquemontii Blume. Journal of Taibah University for Science. 2015;9(4):449–54.CrossRef Baba SA, Malik SA. Determination of total phenolic and flavonoid content, antimicrobial and antioxidant activity of a root extract of Arisaema jacquemontii Blume. Journal of Taibah University for Science. 2015;9(4):449–54.CrossRef
39.
go back to reference Patro G, Bhattamisra SK, Mohanty BK, Sahoo HB. In vitro and in vivo antioxidant evaluation and estimation of total phenolic, flavonoidal content of Mimosa pudica L. Pharm Res. 2016;8(1):22. Patro G, Bhattamisra SK, Mohanty BK, Sahoo HB. In vitro and in vivo antioxidant evaluation and estimation of total phenolic, flavonoidal content of Mimosa pudica L. Pharm Res. 2016;8(1):22.
40.
go back to reference Yingming P, Ying L, Hengshan W, Min L. Antioxidant activities of several Chinese medicine herbs. Food Chem. 2004;88(3):347–50.CrossRef Yingming P, Ying L, Hengshan W, Min L. Antioxidant activities of several Chinese medicine herbs. Food Chem. 2004;88(3):347–50.CrossRef
41.
go back to reference Ghasemzadeh A, Jaafar HZ, Rahmat A. Effects of solvent type on phenolics and flavonoids content and antioxidant activities in two varieties of young ginger (Zingiber officinale roscoe) extracts. J Med Plants Research. 2011;5(7):1147–54. Ghasemzadeh A, Jaafar HZ, Rahmat A. Effects of solvent type on phenolics and flavonoids content and antioxidant activities in two varieties of young ginger (Zingiber officinale roscoe) extracts. J Med Plants Research. 2011;5(7):1147–54.
42.
go back to reference Shi AW, Wang XB, Lu FX, Zhu MM, Kong XQ, Cao KJ. Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation. Acta Pharmacol Sin. 2009;30(3):299–306.CrossRefPubMedPubMedCentral Shi AW, Wang XB, Lu FX, Zhu MM, Kong XQ, Cao KJ. Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation. Acta Pharmacol Sin. 2009;30(3):299–306.CrossRefPubMedPubMedCentral
44.
go back to reference Drużyńska B, Stępniewska A, Wołosiak R. The influence of time and type of solvent on efficiency of the extraction of polyphenols from green tea and antioxidant properties obtained extracts. Acta Sci Pol Technol Aliment. 2007;6(1):27–36. Drużyńska B, Stępniewska A, Wołosiak R. The influence of time and type of solvent on efficiency of the extraction of polyphenols from green tea and antioxidant properties obtained extracts. Acta Sci Pol Technol Aliment. 2007;6(1):27–36.
45.
go back to reference Thoppil RJ, Bishayee A. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World Journal Hepatology. 2011;3(9):228–49.CrossRef Thoppil RJ, Bishayee A. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World Journal Hepatology. 2011;3(9):228–49.CrossRef
46.
go back to reference Huang M, Lu JJ, Huang MQ, Bao JL, Chen XP, Wang YT. Terpenoids: natural products for cancer therapy. Expert Opin Investig Drugs. 2012;21(12):1801–18.CrossRefPubMed Huang M, Lu JJ, Huang MQ, Bao JL, Chen XP, Wang YT. Terpenoids: natural products for cancer therapy. Expert Opin Investig Drugs. 2012;21(12):1801–18.CrossRefPubMed
47.
go back to reference Xu K, Wang P, Yuan B, Cheng Y, Li Q, Lei H. Structural and bioactive studies of terpenes and cyclopeptides from the genus Rubia. Chemistry Central Journal. 2013;7(1):1.CrossRef Xu K, Wang P, Yuan B, Cheng Y, Li Q, Lei H. Structural and bioactive studies of terpenes and cyclopeptides from the genus Rubia. Chemistry Central Journal. 2013;7(1):1.CrossRef
48.
go back to reference Yu L, Perret J, Davy B, Wilson J, Melby CL. Antioxidant properties of cereal products. J Food Sci. 2002;67(7):2600–3.CrossRef Yu L, Perret J, Davy B, Wilson J, Melby CL. Antioxidant properties of cereal products. J Food Sci. 2002;67(7):2600–3.CrossRef
49.
go back to reference Nakamura, M., Ra, J. H., Jee, Y., and Kim, J. S.. Impact of different partitioned solvents on chemical composition and bioavailability of Sasa quelpaertensis Nakai leaf extract. Journal of Food and Drug Analysis (2016). Nakamura, M., Ra, J. H., Jee, Y., and Kim, J. S.. Impact of different partitioned solvents on chemical composition and bioavailability of Sasa quelpaertensis Nakai leaf extract. Journal of Food and Drug Analysis (2016).
Metadata
Title
In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231
Authors
Muhammad Luqman Nordin
Arifah Abdul Kadir
Zainul Amiruddin Zakaria
Rasedee Abdullah
Muhammad Nazrul Hakim Abdullah
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2153-5

Other articles of this Issue 1/2018

BMC Complementary Medicine and Therapies 1/2018 Go to the issue