Hydrolysis product of Nigella A obtained from Nigella glandulifera Freyn seeds promotes apoptosis and AMPK-mediated autophagy in human colon cancer SW620 cells

Authors

  • Lili Chen 1. Wenzhou Medical University, Wenzhou 325035; 2. Department of Oncology, the Hangzhou First People’s Hospital, Hangzhou 310006
  • Haote Han 1. The Key Laboratory of Biomedical Engineering, Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310028; 2. Zhejiang-Malaysia Joint Research Center for Traditional Medicine, Zhejiang University, Hangzhou 310028
  • Awais Amin 1. The Key Laboratory of Biomedical Engineering, Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310028; 2. Zhejiang-Malaysia Joint Research Center for Traditional Medicine, Zhejiang University, Hangzhou 310028
  • Lin Zhang 1. The Key Laboratory of Biomedical Engineering, Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310028; 2. Zhejiang-Malaysia Joint Research Center for Traditional Medicine, Zhejiang University, Hangzhou 310028
  • Shenglin Ma 1. Wenzhou Medical University, Wenzhou 325035; 2. Department of Oncology, the Hangzhou First People’s Hospital, Hangzhou 310006

Keywords:

nigella A, nigella B, apoptosis, autophagy, AMPK, mTOR

Abstract

Paper description:

  • Nigella B (NB) is the hydrolysis product of Nigella A (NA) which is extracted from the seeds of Nigella glandulifera Freyn and has been reported to possess several beneficial characteristics, including an anticancer effect.
  • This work demonstrates for the first time the anticancer effect of NA and the mechanism of NB on inducing autophagy in combination with the apoptotic pathway, in human colon cancer cell lines.
  • Our study reveals an anticancer function for NA and NB in colon cancer and supports the use of NA as an antitumor pro-drug and NB as a novel therapeutic drug.

Abstract: Nigella B (NB) is the hydrolysis product of Nigella A (NA), which is extracted from the seeds of Nigella glandulifera Freyn. NB has several beneficial characteristics, including antiproliferative activity against several cancer cell lines. In this study, we analyzed the in vitro and in vivo anticancer activity of both NA and NB as well as the potential molecular mechanisms behind the actions of NB. We found that NB treatment led to autophagy and soft apoptosis in colon cancer cells (SW620). NA treatment had no effect on either. Further study showed that NB treatment in SW620 cells led to inhibited phosphorylated mammalian target of rapamycin (p-mTOR) expression but increased phosphorylated-5' adenosine monophosphate protein kinase (AMPK) expression, a key regulator of autophagy. This suggests that the AMPK-mTOR pathway plays a crucial role in autophagy induction. Separate in vivo studies using NA (40 mg/kg, intragastric administration (i.g.)) and NB (40 mg/kg, i.g.) resulted in inhibited tumor growth in nude mice by 42.82% and 37.20% respectively, when compared with vehicle-administered animals. In vitro tumor protein expression was consistent with its expression in vitro. Taken together, our results reveal an anticancer function for NA and NB in colon cancer and support the use of NA as an antitumor prodrug, and NB as a novel therapeutic drug.

https://doi.org/10.2298/ABS171108021C

Received: November 8, 2017; Revised: March 30, 2018; Accepted: March 30, 2018; Published online: May 15, 2018

How to cite this article: Chen L, Han H, Amin A, Zhang L, Ma S. Hydrolysis product of Nigella A obtained from Nigella glandulifera Freyn seeds promotes apoptosis and AMPK-mediated autophagy in human colon cancer SW620 cells. Arch Biol Sci. 2018;70(4):603-12.

Downloads

Download data is not yet available.

References

Chang Y, Tseng H, Huang C, Chen Y, Chiang H, Chou F. Relative down-regulation of apoptosis and autophagy genes in colorectal cancer. Clin Invest. 2011;41(1):84-92.

Li J, Hou N, Faried A, Tsutsumi S, Kuwano H. Inhibition of autophagy augments 5-fluorouracil chemotherapy in human colon cancer in vitro and in vivo model. Eur J Cancer. 2010;46(10):1900-9.

Beretta G, Pessi M, Poletti P, Mosconi S, Labianca R. New drugs and combinations in the palliative treatment of colon and rectal cancer. Surg Oncol. 2001;27(6):595-600.

Bursch W, Hochegger K, Torok L, Marian B, Ellinger A, Hermann R. Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. Cell Sci. 2000;113(7):1189-98.

Kelekar A. Autophagy. Ann N Y Acad Sci. 2006;1066(1):259-71.

Lin L, Dawson P, Richardson C. Viral interactions with macroautophagy: a double-edged sword. Virology. 2010;402(1):1-10.

Jaeger PA, Wyss-Coray T. All you can eat: autophagy in neurodegeneration and neuroprotection. Mol Neurodegener. 2009;4(1):1-22.

Giannopoulou E, Antonacopoulou A, Matsouka P, Kalofonos H. Autophagy: novel action of panitumumab in colon cancer. Anticancer Res. 2009;29(12):5077-82.

Wang N, Feng Y, Zhu M, Tsang C, Man K, Tong Y, Tsao S. Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism. J Cell Biochem. 2010;111(6):1426-36.

Mohamed L. Immunomodulatory and therapeutic properties of the Nigella sativa L. Seed. Int Immunopharmacol. 2005;5(13-14):1749-70.

Fico G, Panizzi L, Fiamini G, Braca A, Morelli I, Tomè F, Cioni P. Biological screening of Nigella damascena for antimicrobial and molluscicidal activities. Pyhtother Res. 2004;18(6):468-70.

Ali B, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Pyhtother Res. 2003;17(4):299-305.

Li W, Yan X, Sun Y, Ngan T, Shim S, Kim Y. Anti-Inflammatory and PPAR Transactivational Effects of Oleanane-Type Triterpenoid Saponins from the Roots of Pulsatillakoreana. Biomol Ther. 2014; 22(4):334-40.

Zhao M, Da-Wa Z, Guo D, Fang D, Chen X, Xu H, Gu Y, Xia B, Chen L, Ding L, Zhou Y. Cytotoxic triterpenoid saponins from Clematis tangutica. Phytochemistry. 2016;130:228-37.

Liu J, Guan Y, Zou L, Gong Y, Hua H, Xu Y, Zhang H, Yu Z, Fan W H. Saponins with Neuroprotective Effects from the Roots of Pulsatillacernua. Molecules. 2012;17(5):5520-31.

Han HT, Liu N, Zhang L, Gong MH, Cao M, Li BG, Kaisa S, Yu XY, Tian JK. Promotion of cytoplasmic vacuolation-mediated cell death of human prostate cancer PC-3 cells by oxidative stress induced by daucusol, a new guaiane-type sesquiterpenoid from Daucuscarota L. Arch Biol Sci. 2017;69(3):481-9.

Suárez Y, González L, Cuadrado A. Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells. Mol Cancer Ther. 2003;2(9):863-72.

DiPaola RS, Dvorzhinski D, Thalasila A, Garikapaty V, Doram D, May M, Bray K, Mathew R, Beaudoin B, Karp C, Stein M, Foran DJ, White E. Therapeutic Starvation and Autophagy in Prostate Cancer: A New Paradigm for Targeting Metabolism in Cancer Therapy. Prostate. 2008;68(16):1743-52.

Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt S, King R, Cibas E, Brugge J. A nonapoptotic cell death process, entosis, that occurs by Cell-in-Cell invasion. Cell. 2007;131(5):966-79.

Almagro MCD, Vucic D. Necroptosis: Pathway diversity and characteristics. Semin Cell Dev Biol. 2015;39:56-62.

Kirkegaard K, Taylor MP, Jackson WT. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nat Rev Microbiol. 2004;2(4):301-14.

Kondo Y, Kanzawa T, Sawaya R, Kondo S. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005;5(9):726-34.

Tanida I, Minematsu-Ikeguchi N, Ueno T, Kominami E. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy. 2005;1(2):84-91.

Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Oshumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Embo J. 2000;19(21):5720-8.

Meley D, Bauvy C, Houben-Weerts JH, Dubbelhuis P, Helmond MT, Codogno P, Meijer AJ. AMP activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem. 2006;281(46):34870-9.

Herrero-Martin G, Hoyer-Hansen M, Garcia-Garcia C, Fumarola C, Farkas T, Lopez-Rivas A, Jaattela M. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. Embo J. 2009;28(6):677-85.

Neuzil J, Weber T, Schroder A, Lu M, Ostermann G, Gellert N, Mayne GC, Olejnicka B, Negre-Salvayre A, Sticha M, Coffey RJ, Weber C. Induction of cancer cell apoptosis by alphatocopheryl succinate: molecular pathways and structural requirements. FASEB J. 2001;15(2):403-15.

Sun Y, Zhao Y, Hou L, Zhang X, Zhang Z, Wu K. RRRalpha- tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-kappaB signaling pathway. Oncol Rep. 2014;32(3):1243-8.

Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741-52.

Mariño G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 2014;15(2):81-94.

Downloads

Published

2018-12-04

How to Cite

1.
Chen L, Han H, Amin A, Zhang L, Ma S. Hydrolysis product of Nigella A obtained from Nigella glandulifera Freyn seeds promotes apoptosis and AMPK-mediated autophagy in human colon cancer SW620 cells. Arch Biol Sci [Internet]. 2018Dec.4 [cited 2024Apr.24];70(4):603-12. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/2351

Issue

Vol. 70 No. 4 (2018)

Section

Articles

License

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.