Chemopreventive and immunomodulatory effects of Murraya koenigii aqueous extract on 4T1 breast cancer cell-challenged mice

BMC Complementary and Alternative Medicine

Noorjahan Banu Alitheen⁴  Sheau Wei Tan¹  Huynh Ky³  Hamidah Mohd Yusof¹  Siamak Ebrahimi¹  Wan Yong Ho⁵  Boon Kee Beh²  Nurul Elyani Mohamad⁴  Nadiah Abu⁴  Swee Keong Yeap¹ 

[1] Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia;Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia;Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, 3/2 Street, Can Tho City, Vietnam;Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia;School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Jalan Broga, Semenyih, 43500, Selangor, Malaysia

关键词: 4T1 cells;    Murraya koenigii;    Curry leaves;    Chemopreventive;    Anti-inflammation;   

Others  :  1224060
DOI  :  10.1186/s12906-015-0832-z

 received in 2015-06-19, accepted in 2015-08-26,  发布年份 2015

【 摘 要 】

Background

The progression of breast cancer is increasing at an alarming rate, particularly in western countries. Meanwhile, the lower incidence in Asian countries could be attributed to the heavy incorporation of green leaves vegetables or spices in their diets. Murraya koenigii (MK) or often times known as curry leaves are common spice used mostly in tropical countries. Anti-inflammatory and chemopreventive effects of MK aqueous extract on 4T1 breast cancer cell-challenged mice were evaluated.

Methods

Herein, cytotoxic activity of MK was first tested on 4T1 cells in vitroby MTT assay. Then, in vivo chemopreventive study was conducted where mice were fed with extracts prior to and after inducing the tumor (inoculation). Tumor size was monitored post-4T1 inoculation. At the end of experiment, histopathology of tumor sections, T cell immunophenotyping, tumor nitric oxide level, serum cytokine level and qPCR analysis on expression of iNOS, iCAM, NF-kB and c-MYC were performed.

Results

MK reduced the tumors’ size and lung metastasis aside from inhibited the viability of 4T1 cells in vitro. Furthermore, it decreased the level of nitric oxide and inflammation-related cytokines and genes, including iNOS, iCAM, NF-kB and c-MYC.

Conclusion

The results propose that, MK managed to inhibit the progression of tumor via immunostimulatory effect and inflammatory reaction within the tumor samples. This suggests that MKconsumption could be a savior in the search of new chemopreventive agents.

【 授权许可】

   
2015 Yeap et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Fig. 7.

【 参考文献 】

• [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90.
• [2]Luk S-U, Lee TK-W, Liu J, Lee DT-W, Chiu Y-T, Ma S, Ng IO-L, Wong Y-C, Chan FL, Ling M-T. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population. PLoS One. 2011; 6(5):e19804.
• [3]Li Y, Brown PH. Prevention of ER-negative breast cancer. Recent results in cancer research Fortschritte der Krebsforschung Progres dans les recherches sur le cancer. 2009; 181:121-134.
• [4]Ho B-Y, Lin C-H, Apaya MK, Chao W-W, Shyur L-F. Silibinin and paclitaxel cotreatment significantly suppress the activity and lung metastasis of triple negative 4T1 mammary tumor cell in mice. J Tradit Complement Med. 2012; 2(4):301.
• [5]Zhang M, Hettiarachchy NS, Horax R, Kannan A, Praisoody A, Muhundan A, Mallangi CR. Phytochemicals, antioxidant and antimicrobial activity of Hibiscus sabdariffa, Centella asiatica, Moringa oleifera and Murraya koenigii leaves. J Med Plants Res. 2011; 5(30):6672-6680.
• [6]Noolu B, Ajumeera R, Chauhan A, Nagalla B, Manchala R, Ismail A. Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells. BMC Complement Altern Med. 2013; 13(1):7. BioMed Central Full Text
• [7]Ghasemzadeh A, Jaafar HZE, Rahmat A, Devarajan T. Evaluation of bioactive compoudns, pharmaceutical quality, and anticancer activity of curry leaf (Murraya koenigii L.). Evidence-based Complement Altern Med. 2014; 2014:873803.
• [8]Bhattacharya K, Samanta SK, Tripathi R, Mallick A, Chandra S, Pal BC, Shaha C, Mandal C. Apoptotic effects of mahanine on human leukemic cells are mediated through crosstalk between Apo-1/Fas signaling and the Bid protein and via mitochondrial pathways. Biochem Pharmacol. 2010; 79(3):361-372.
• [9]Khan BA, Abraham A, Leelamma S. Murraya koenigii and Brassica juncea—Alterations on lipid profile in 1–2 dimethyl hydrazine induced colon carcinogenesis. Investig New Drugs. 1996; 14(4):365-369.
• [10]Muthumani P, Venkatraman S, Ramseshu K, Meera R, Devi P, Kameswari B, Eswarapriya B. Pharmacological studies of anticancer, anti inflammatory activities of Murraya koenigii (Linn) Spreng in experimental animals. J Pharm Sci Res. 2009; 1:137-141.
• [11]Naik SK, Mohanty S, Padhi A, Pati R, Sonawane A. Evaluation of antibacterial and cytotoxic activity of Artemisia nilagirica and Murraya koenigii leaf extracts against mycobacteria and macrophages. BMC Complement Altern Med. 2014; 14:87. BioMed Central Full Text
• [12]Gupta S, Prakash J. Studies on Indian green leafy vegetables for their antioxidant activity. Plant Foods Hum Nutr. 2009; 64(1):39-45.
• [13]Shah AS, Wakade AS, Juvekar AR. Immunomodulatory activity of methanolic extract of Murraya koenigii (L) Spreng. leaves. Indian J Exp Biol. 2008; 46(7):505-509.
• [14]Bhandari PR. Curry leaf (Murraya koenigii) or cure leaf: review of its curative properties. J Med Nutr Nutraceuticals. 2012; 1(2):92.
• [15]Ito C, Itoigawa M, Nakao K, Murata T, Tsuboi M, Kaneda N, Furukawa H. Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii. Phytomedicine. 2006; 13(5):359-365.
• [16]Syam S, Abdul AB, Sukari MA, Mohan S, Abdelwahab SI, Wah TS. The growth suppressing effects of girinimbine on HepG2 involve induction of apoptosis and cell cycle arrest. Molecules. 2011; 16(8):7155-7170.
• [17]Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011; 10(12):1-19.
• [18]Baliga MS, Meleth S, Katiyar SK. Growth inhibitory and antimetastatic effect of green tea polyphenols on metastasis-specific mouse mammary carcinoma 4T1 cells in vitro and in vivo systems. Clin Cancer Res. 2005; 11(5):1918-1927.
• [19]Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008; 2008:pdb.prot4986.
• [20]Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001; 29(9):e45.
• [21]Chen SS, Corteling R, Stevanato L, Sinden J. Polyphenols inhibit indoleamine 3, 5-dioxygenase-1 enzymatic activity—a role of immunomodulation in chemoprevention. Discov Med. 2012; 14(78):327-333.
• [22]Schäfer G, Kaschula CH. The immunomodulation and anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention. Anti Cancer Agents Med Chem. 2014; 14(2):233.
• [23]Ding ZC, Zhou G. Cytotoxic chemotherapy and CD4+ effector T cells: an emerging alliance for durable antitumor effects. Clin Dev Immunol. 2012; 2012:890178.
• [24]Mohamed MM, Al-Raawi D, Sabet SF, El-Shinawi M. Inflammatory breast cancer: New factors contribute to disease etiology: A review. J Adv Res. 2014; 5(5):525-536.
• [25]Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol. 2005; 78(5):1043-1051.
• [26]Changkija B, Konwar R. Role of interleukin-10 in breast cancer. Breast Cancer Res Treat. 2012; 133(1):11-21.
• [27]Kozłowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz M. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Roczniki Akademii Medycznej w Bialymstoku (1995). 2003; 48:82-84.
• [28]Surh Y-J, Chun K-S, Cha H-H, Han SS, Keum Y-S, Park K-K, Lee SS. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2001; 480:243-268.
• [29]Redelman D, Hunter KW. Microenvironment of the murine mammary carcinoma 4T1: Endogenous IFN-γ affects tumor phenotype, growth, and metastasis. Exp Mol Pathol. 2008; 85(3):174-188.
• [30]van Riggelen J, Felsher DW. Myc and a Cdk2 senescence switch. Nat Cell Biol. 2010; 12(1):7-9.