DOI QR코드

DOI QR Code

Methanol Extract of Flacourtia indica Aerial Parts Induces Apoptosis via Generation of ROS and Activation of Caspases in Human Colon Cancer HCT116 Cells

  • Published : 2014.09.15

Abstract

Different plant parts of Flacourtia indica have long been used in Ayurvedic medicine. Previous studies have demonstrated that the methanolic extract of F. indica possess anti-inflammatory properties. The present study was aimed at investigating the anticancer effects of methanol extract of Flacourtia indica (FIM) aerial parts in human colon cancer (HCT116) cells. Treatment of cells with FIM at a concentration of $500{\mu}g/ml$ for 24 hours significantly reduced cell viability and induced apoptosis, which was associated with the increased cytoplasmic expression of cytochrome c, activation of caspase-3, and the cleavage of poly-(ADP-ribose) polymerase. Incubation with FIM also inhibited the levels of Bcl-2, Bcl-xl and survivin, which are the markers of cell proliferation, whereas the expression of Bax remained unchanged. Treatment with FIM led to the generation of reactive oxygen species (ROS) in a concentration-dependent manner. Pharmacological inhibition of ROS generation by pretreatment of cells with N-acetyl cysteine abrogated FIM-induced apoptosis in HCT116 cells. Thus, these results demonstrate that FIM has anti-proliferative and pro-apoptotic effects in HCT116 cells and the effects are, at least in part, due to the ROS dependent activation of caspases.

Keywords

References

  1. Abdull Razis AF, Noor NM (2013). Cruciferous vegetables: dietary phytochemicals for cancer prevention. Asian Pac J Cancer Prev, 14, 1565-70. https://doi.org/10.7314/APJCP.2013.14.3.1565
  2. Altieri DC (2003). Survivin in apoptosis control and cell cycle regulation in cancer. Prog Cell Cycle Res, 5, 447-52.
  3. Asanuma K, Tsuji N, Endoh T, Yagihashi A, Watanabe N (2004). Survivin enhances Fas ligand expression via up-regulation of specificity protein 1-mediated gene transcription in colon cancer cells. J Immunol, 172, 3922-9. https://doi.org/10.4049/jimmunol.172.6.3922
  4. Banjerdpongchai R, Kongtawelert P (2011). Ethanolic extract of fermented Thunb induces human leukemic HL-60 and Molt-4 cell apoptosis via oxidative stress and a mitochondrial pathway. Asian Pac J Cancer Prev, 12, 2871-4.
  5. Banjerdpongchai R, Punyati P, Nakrob A, Pompimon W, Kongtawelert P (2011). 4'-Hydroxycinnamaldehyde from Alpinia galanga (Linn.) induces human leukemic cell apoptosis via mitochondrial and endoplasmic reticulum stress pathways. Asian Pac J Cancer Prev, 12, 593-8.
  6. Bonnotte B, Favre N, Moutet M, et al (1998). Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors. J Immunol, 161, 1433-8.
  7. Borner C (2003). The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol, 39, 615-47. https://doi.org/10.1016/S0161-5890(02)00252-3
  8. Chun KS, Kim EH, Lee S, Hahm KB (2013). Chemoprevention of gastrointestinal cancer: the reality and the dream. Gut Liver, 7, 137-49. https://doi.org/10.5009/gnl.2013.7.2.137
  9. Earnshaw WC, Martins LM, Kaufmann SH (1999). Mammalian caspases: structure, activation, substrates and functions during apoptosis. Annu Rev Biochem, 68, 383-424. https://doi.org/10.1146/annurev.biochem.68.1.383
  10. Eramma N, Devaraja G (2013). Antibacterial potential and phytochemical analysis of Flacourtia indica (Burm.f.) Merr. root extract against human pathogens. Indo Am J Pharm Res, 3, 3832-46.
  11. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74. https://doi.org/10.1016/j.cell.2011.02.013
  12. Hasan TN, Leena GB, Shafi G, Al-Hazzani AA, Alshatwi AA (2011). Anti-proliferative effects of organic extracts from root bark of Juglans Regia L. (RBJR) on MDA-MB-231 human breast cancer cells: role of Bcl-2/Bax, caspases and Tp53. Asian Pac J Cancer Prev, 12, 525-30.
  13. Jang SI, Kim YJ, Lee WY, et al (2005). Scoparone from Artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-gamma Plus LPS. Arch Pharm Res, 28, 203-8. https://doi.org/10.1007/BF02977716
  14. Janicke RU, Sprengart ML, Wati MR, Porter AG (1998). Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem, 273, 9357-60. https://doi.org/10.1074/jbc.273.16.9357
  15. Kamangar F, Dores GM, Anderson WF (2006). Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol, 24, 2137-50. https://doi.org/10.1200/JCO.2005.05.2308
  16. Kaou AM, Mahiou-Leddet V, Canlet C, et al (2010). Antimalarial compounds from the aerial parts of Flacourtia indica (Flacourtiaceae). J Ethnopharmacol, 130, 272-4. https://doi.org/10.1016/j.jep.2010.04.045
  17. Kim HS, Kundu JK, Lee JS, et al (2008). Chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica on azoxymethane-initiated and dextran sulfate sodium-promoted mouse colon carcinogenesis. Nutr Cancer, 60, 90-7. https://doi.org/10.1080/01635580802404170
  18. Kim JK, Kim JY, Kim HJ, et al (2013). Scoparone exerts antitumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity. PLoS One, 8, e80391. https://doi.org/10.1371/journal.pone.0080391
  19. Kundu J, Roy M, Bachar SC, Chun KS, Kundu JK (2013). Analgesic, anti-inflammatory, and diuretic activity of methanol extract of Flacourtia indica. Arch Basic Appl Med, 1, 39-44.
  20. Kundu J, Wahab SM, Kundu JK, et al (2012). Tob1 induces apoptosis and inhibits proliferation, migration and invasion of gastric cancer cells by activating Smad4 and inhibiting betacatenin signaling. Int J Oncol, 41, 839-48.
  21. Kundu JK, Surh YJ (2005). Breaking the relay in deregulated cellular signal transduction as a rationale for chemoprevention with anti-inflammatory phytochemicals. Mutat Res, 591, 123-46. https://doi.org/10.1016/j.mrfmmm.2005.04.019
  22. Moghimi-Dehkordi B, Safaee A (2012). An overview of colorectal cancer survival rates and prognosis in Asia. World J Gastrointest Oncol, 4, 71-5. https://doi.org/10.4251/wjgo.v4.i4.71
  23. Nazneen N, Mazid MA, Kundu JK, et al (2009). Protective effects of Flacourtia indica aerial parts extract against paracetamol-induced hepatotoxicity in rats. J Taibah Univ Sci, 2, 1-6. https://doi.org/10.1016/S1658-3655(12)60001-6
  24. Nazneen N, Mazid MA, Kundu JK, et al (2002). Phytochemical and Biological studies of Flacourtia indica. Dhaka Univ J Biol Sci, 11, 183-7.
  25. Pal SK, Shukla Y (2003). Herbal medicine: current status and the future. Asian Pac J Cancer Prev, 4, 281-8.
  26. Sehitoglu MH, Farooqi AA, Qureshi MZ, Butt G, Aras A (2014). Anthocyanins: targeting of signaling networks in cancer cells. Asian Pac J Cancer Prev, 15, 2379-81. https://doi.org/10.7314/APJCP.2014.15.5.2379
  27. Shukla Y, Pal SK (2004). Complementary and alternative cancer therapies: past, present and the future scenario. Asian Pac J Cancer Prev, 5, 3-14.
  28. Vayghan HJ, Ghadimi SS, Nourazarian AR (2014). Preventive and therapeutic roles of ginseng - focus on colon cancer. Asian Pac J Cancer Prev, 15, 585-8. https://doi.org/10.7314/APJCP.2014.15.2.585
  29. Yeh CC, Yang JI, Lee JC, et al. (2012). Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress. BMC Complement Altern Med, 12, 142. https://doi.org/10.1186/1472-6882-12-142

Cited by

  1. The caspase 3-dependent apoptotic effect of pycnogenol in human oral squamous cell carcinoma HSC-3 cells vol.58, pp.1, 2016, https://doi.org/10.3164/jcbn.15-7
  2. Anticancer effect of icaritin inhibits cell growth of colon cancer through reactive oxygen species, Bcl-2 and cyclin D1/E signaling vol.12, pp.5, 2016, https://doi.org/10.3892/ol.2016.5089
  3. anti-proliferative activity vol.6, pp.4, 2019, https://doi.org/10.1088/2053-1591/aafa9b
  4. Investigation of phytochemical constituents of anti-leukemic herbal drugs used by the traditional healers of Purulia, Birbhum and Bankura districts of West Bengal pp.1478-6427, 2019, https://doi.org/10.1080/14786419.2019.1566818