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Suppression of Human Fibrosarcoma Cell Metastasis by Phyllanthus emblica Extract in Vitro

  • Yahayo, Waraporn (Department of Physiology, Faculty of Medicine, Srinakharinwirot University) ;
  • Supabphol, Athikom (Department of Surgery, Faculty of Medicine, HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC), Srinakharinwirot University) ;
  • Supabphol, Roongtawan (Department of Physiology, Faculty of Medicine, Srinakharinwirot University)
  • Published : 2013.11.30

Abstract

Phyllanthus emblica (PE) is known to exhibit various pharmacological properties. This study aimed to evaluate the antimetastatic potential of a PE aqueous extract. Cytotoxicity to human fibrosarcoma cells, HT1080, was determined by viability assay using the 3-(4,5-dimethylthiazol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Cell migration and invasion were investigated using chemotaxis chambers containing membranes precoated with collagen IV and Matrigel, respectively. Cell attachment onto normal surfaces of cell culture plates was tested to determine the cell-adhesion capability. The molecular mechanism of antimetastatic activity was assessed by measuring the gene expression of matrix metalloproteinases, MMP2, and MMP9, using reverse transcription-polymerase chain reaction (RT-PCR) assay. The mRNA levels of both genes were significantly down-regulated after pretreatment with PE extract for 5 days. Our findings show the antimetastatic function of PE extract in reducing cell proliferation, migration, invasion, and adhesion in both dose- and time-dependent manners, especially growth arrest with low $IC_{50}$ value. A decrease in the expression of both MMP2 and MMP9 seems to be the cellular mechanism for antimetastasis in this case. There is a high potential to use PE extracts clinically as an optional adjuvant therapeutic drug for therapeutic intervention strategies in cancer therapy or chemoprevention.

Keywords

Phyllanthus emblica;migration;invasion;adhesion;metastasis

References

  1. Baliga MS (2010). Triphala, Ayurvedic formulation for treating and preventing cancer: a review. J Altern Complement Med, 16, 1301-8. https://doi.org/10.1089/acm.2009.0633
  2. Baliga MS, Dsouza JJ (2011). Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer. Eur J Cancer Prev, 20, 225-39. https://doi.org/10.1097/CEJ.0b013e32834473f4
  3. Catalano V, Turdo A, Di Franco S, et al (2013). Tumor and its microenvironment: a synergistic interplay. Semin Cancer Biol, [Epub ahead of print].
  4. Chanvorachote P, Pongrakhananon V, Luanpitpong S, et al (2009). Type I pro-collagen promoting and anti-collagenase activities of Phyllanthus emblica extract in mouse fibroblasts. J Cosmet Sci, 60, 395-403.
  5. Charoenteeraboon J, Ngamkitidechakul C, Soonthornchareonnon N, Jaijoy K, Sireeratawong S (2010). Antioxidant activities of the standardized water extract from fruit of Phyllanthus emblica Linn. Songklanakarin J Sci Technol, 32, 599-604.
  6. Chen KH, Lin BR, Chien CT, Ho CH (2011). Emblica officinalis Gaertn. attentuates N-nitrosodiethylamine-induced apoptosis, autophagy, and inflammation in rat livers. J Med Food, 14, 746-55. https://doi.org/10.1089/jmf.2010.1459
  7. De A, De A, Papasian C, et al (2013). Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors. PLoS ONE, 8, 72748. https://doi.org/10.1371/journal.pone.0072748
  8. Fujii T, Wakaizumi M, Ikami T, Saito M (2008). Amla (Emblica officinalis Gaertn.) extract promotes procollagen production and inhibits matrix metalloproteinase-1 in human skin fibroblasts. J Ethnopharmacol, 119, 53-7. https://doi.org/10.1016/j.jep.2008.05.039
  9. Hassan ZK, Elamin MH, Daghestani MH, et al (2012). Oleuropein induces anti-metastatic effects in breast cancer. Asian Pac J Cancer Prev, 13, 4555-9. https://doi.org/10.7314/APJCP.2012.13.9.4555
  10. Huabprasert S, Kasetsinsombat K, Kangsadalampai K, et al (2012). The Phyllanthus emblica L. infusion carries immunostimulatory activity in a mouse model. J Med Assoc Thai, 95, 75-82.
  11. Huang JL, Zhong ZG (2011). Study of galic acid extracted from the leaves of Phyllanthus emblica on apoptotic mechanism of human hepatocellular carcinoma cells BEL-7404. Zhong Yao Cai, 34, 246-9.
  12. Jain DP, Pancholi SS, Patel R (2011). Synergistic antioxidant activity of green tea with some herbs. J Adv Pharm Technol Res, 2, 177-83. https://doi.org/10.4103/2231-4040.85538
  13. Jindal A, Soyal D, Sharma A, Goyal PK (2009). Protective effect of an extract of Emblica officinalis against radiation-induced damage in mice. Integr Cancer Ther, 8, 98-105. https://doi.org/10.1177/1534735409331455
  14. Krishnaveni M, Mirunalini S (2011). Amla . The role of Ayurvedic therapeutic herb in cancer. Asian J Pharm Clin Res, 4, 13-7.
  15. Lee SH, Jaganath IB, Wang SM, Sekaran SD (2011). Antimetastatic effects of Phyllanthus on human lung (A549) and breast (MCF-7) cancer cell lines. PLoS ONE, 6, 20994. https://doi.org/10.1371/journal.pone.0020994
  16. Liu X, Zhao M, Wang J, Yang B, Jiang Y (2008). Antioxidant activity of methanolic extract of emblica fruit (Phyllanthus emblica L.) from six regions in China. J Food Comp Anal, 21, 219-28. https://doi.org/10.1016/j.jfca.2007.10.001
  17. Majeed M, Bhat B, Anand S, et al (2011). Inhibition of UV-induced ROS and collagen damage by Phyllanthus emblica extract in normal human dermal fibroblasts. J Cosmet Sci, 62, 49-56.
  18. Naik GH, Priyadarsini KI, Bhagirathi RG, et al (2005). In vitro antioxidant studies and free radical reactions of triphala, an ayurvedic formulation and its constituents. Phytother Res, 19, 582-6. https://doi.org/10.1002/ptr.1515
  19. Ngamkitidechakul C, Jaijoy K, Hansakul P, Soonthornchareonnon N, Sireeratawong S (2010). Antitumour effects of Phyllanthus emblica L.: Induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion of human cancer cells. Phytother Res, 24, 1405-13. https://doi.org/10.1002/ptr.3127
  20. Pinmai K, Chunlaratthanabhorn S, Ngamkitidechakul C, Soonthornchareon N, Hahnvajanawong C (2008). Synergistic growth inhibitory effects of Phyllanthus emblica and terminalia bellerica extracts with conventional cytotoxic agents: doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells. World J Gastroenterol, 14, 1491-7. https://doi.org/10.3748/wjg.14.1491
  21. Said G, Guilbert M, Millerot-Serrurot E, et al (2012). Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells. Int J Oncol, 40, 1797-804.
  22. Shivananjappa MM, Joshi MK (2012). Influence of Emblica officinalis aqueous extract on growth and antioxidant defense system of human hepatoma cell line (HepG2). Pharm Biol, 50, 497-505. https://doi.org/10.3109/13880209.2011.618501
  23. Supabphol A, Muangman V, Chavasiri W, Supabphol R, Gritsanapan W (2009). N-acetylcysteine inhibits proliferation, adhesion, migration and invasion of human bladder cancer cells. J Med Assoc Thai, 92, 1171-7.
  24. Zhong ZG, Wu DP, Huang JL, et al (2011). Progallin A isolated from the acetic ether part of the leaves of Phyllanthus emblica L. induces apoptosis of human hepatocellular carcinoma BEL-7404 cells by up-regulation of Bax expression and down-regulation of Bcl-2 expression. J Ethnopharmacol, 133, 765-72. https://doi.org/10.1016/j.jep.2010.11.001

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