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Biologia

, Volume 74, Issue 2, pp 187–193 | Cite as

Caulerpa taxifolia inhibits cell proliferation and induces oxidative stress in breast cancer cells

  • Richa Mehra
  • Satej Bhushan
  • Umesh Prasad Yadav
  • Felix Bast
  • Sandeep SinghEmail author
Original Article
  • 19 Downloads

Abstract

Caulerpa taxifolia (M. Vahl) C. Agardh or killer alga is known to possess several bioactive secondary metabolites with unique structural modifications. We investigated anti-oxidant and anti-proliferative activity of C. taxifolia extract (CTE) on breast and lung cancer cells, along with possible effects on mitochondrial membrane potential (MMP) and cell cycle progression. The results revealed up to 6-folds increase in reactive oxygen species (ROS), 2-folds increase in glutathione reductase (GR) activity, 1.7-fold increase in superoxide dismutase (SOD) activity and 1.8-fold change in catalase activity w.r.t. untreated cells i.e. 10.72 to 21.44 nmol/min/mL, 2.0 to 3.49 U/mL and 37.51 to 69.26 U/min/g FW, respectively, in MDA-MB-cells. Likewise, selective anti-proliferative activity with IC50 0.19 + 0.1, 0.27 + 0.1, and 0.43 + 0.1 μg/μL, was recorded in MDA-MB-231, T-47D, and H1299 cells. In addition, dose-dependent increase in MMP of up to 40% and G1/S phase mitotic arrest was documented by CTE treatment in MDA-MB-231 cells. The results suggest an anti-proliferative and oxidative stress inducing activity of CTE. Changes in MMP and cell cycle arrest further support the anti-cancer effects of CTE. It is believed that C. taxifolia may be considered as a potent source of anti-cancer drugs, subject to further validations.

Keywords

Caulerpa taxifolia Marine alga Killer alga Cancer Oxidative stress 

Abbreviations

CTE

Caulerpa taxifolia extract

CYN

Caulerpenyne

ROS

Reaction oxygen species

MMP

Mitochondrial membrane potential

GR

Glutathione reductase

SOD

Superoxide dismutase

hPBMCs

Human peripheral blood mononuclear cells

JC-1

5,5’,6,6’-tetraethylbenzimidazolylcarbocyanine iodide

DMEM

Dulbecco’s modified eagle medium

DMSO

dimethylsulfoxide

PBS

phosphate saline buffer

MTT

3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Notes

Acknowledgments

All authors acknowledge Central University of Punjab, for providing the necessary infrastructure and resources.

Authors’ contributions

RM and SB conducted all the lab experiments. UPY did cell cycle analysis. SS designed the experiments and all authors contributed in writing the manuscript. The final manuscript is read and approved by all authors.

Funding

RM acknowledges Indian Council of Medical Research (ICMR), India, for providing financial assistance as Junior Research Fellowship. SB acknowledges Ministry of Earth Sciences, India-Drugs from Sea programme (MoES-DFS) for financial assistance. UPY acknowledges CSIR for providing PhD fellowship (CSIR-JRF). FB acknowledges MoES-DSF for research grant. SS acknowledges Department of Science & Technology, India-Science and Engineering Research Board (DST-SERB) extra mural grant for financial assistance.

Compliance with ethical standards

Ethics approval and consent to participate

Not Applicable.

Consent for publication

Not Applicable.

Competing interests

The authors declare that they have no competing interests.

References

  1. Aebi H (1984) Catalase in vitro. In: Methods in enzymology, vol 105. Elsevier, pp 121–126.  https://doi.org/10.1016/S0076-6879(84)05016-3
  2. Alex JM, Singh S, Kumar R (2014) 1-Acetyl-3, 5-diaryl-4, 5-dihydro (1H) pyrazoles: exhibiting anticancer activity through intracellular ROS scavenging and the mitochondria-dependent death pathway. Arch Pharm 347:717–727.  https://doi.org/10.1002/ardp.201400199 CrossRefGoogle Scholar
  3. Aplikioti M et al (2016) Further expansion of the alien seaweed Caulerpa taxifolia var. distichophylla (Sonder) Verlaque, Huisman & Procacini (Ulvophyceae, Bryopsidales) in the eastern Mediterranean Sea. Aquat Invasions 11:11–20.  https://doi.org/10.3391/ai.2016.11.1.02 CrossRefGoogle Scholar
  4. Barbier P, Guise S, Huitorel P, Amade P, Pesando D, Briand C, Peyrot V (2001) Caulerpenyne from Caulerpa taxifolia has an antiproliferative activity on tumor cell line SK-N-SH and modifies the microtubule network. Life Sci 70:415–429.  https://doi.org/10.1016/S0024-3205(01)01396-0 CrossRefGoogle Scholar
  5. Bhushan S, Mehra R, Rani P, Bast F (2016) DB IndAlgae: an on-line resource of marine algae from India identified on the basis of molecular and morphological features. Curr Sci (00113891) 111.  https://doi.org/10.18520/cs/v111/i4/723-726
  6. Cao J et al (2007) Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. Free Radic Biol Med 43:968–975.  https://doi.org/10.1016/j.freeradbiomed.2007.06.006 CrossRefGoogle Scholar
  7. Carlberg I, Mannervik B (1985) Glutathione reductase. In: Methods in enzymology, vol 113. Elsevier, pp 484–490.  https://doi.org/10.1016/S0076-6879(85)13062-4
  8. Cavas L, Yurdakoc K (2005) A comparative study: assessment of the antioxidant system in the invasive green alga Caulerpa racemosa and some macrophytes from the Mediterranean. J Exp Mar Biol Ecol 321:35–41.  https://doi.org/10.1016/j.jembe.2004.12.035 CrossRefGoogle Scholar
  9. Chou ST, Lin HC, Chuang MY, Chiu TH (2014) Treatment with Caulerpa Microphysa pepsin-digested extract induces apoptosis in murine leukemia WEHI-3 cells. J Food Biochem 38:469–479  https://doi.org/10.1111/jfbc.12079 CrossRefGoogle Scholar
  10. Dra M, Ribera A, IUCN/SSC-ISSG (2018) Global Invasive Species Database: Caulerpa taxifolia. IUCN. http://www.iucngisd.org/gisd/speciesname/Caulerpa+taxifolia on 01-02-2018. Accessed 01-12-2018
  11. Draganov D et al (2015) Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death. Sci Rep 5:16222.  https://doi.org/10.1038/srep16222 CrossRefGoogle Scholar
  12. Farooqi AA et al (2015) Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress. Tumor Biol 36:5743–5752.  https://doi.org/10.1007/s13277-015-3797-0 CrossRefGoogle Scholar
  13. Fischel J et al (1995) Cell growth inhibitory effects of caulerpenyne, a sesquiterpenoid from the marine algae Caulerpa taxifolia. Anticancer Res 15:2155–2160Google Scholar
  14. Ghasemzadeh A, Ghasemzadeh N (2011) Flavonoids and phenolic acids: role and biochemical activity in plants and human. J Med Plants Res 5:6697–6703.  https://doi.org/10.5897/JMPR11.1404 Google Scholar
  15. Gross H, König GM (2006) Terpenoids from marine organisms: unique structures and their pharmacological potential. Phytochem Rev 5:115–141.  https://doi.org/10.1007/s11101-005-5464-3 CrossRefGoogle Scholar
  16. Guiry M, Guiry G (2016) AlgaeBase. World-wide electronic publication, National University of Ireland, Galway. 2015 URL: http://www.algaebase.org
  17. Harvey AL, Edrada-Ebel R, Quinn RJ (2015) The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 14:111.  https://doi.org/10.1038/nrd4510 CrossRefGoogle Scholar
  18. Joshi G, Amrutkar SM, Baviskar AT, Kler H, Singh S, Banerjee UC, Kumar R (2016) Synthesis and biological evaluation of new 2, 5-dimethylthiophene/furan based N-acetyl pyrazolines as selective topoisomerase II inhibitors. RSC Adv 6:14880–14892.  https://doi.org/10.1039/c5ra25705k CrossRefGoogle Scholar
  19. Joshi G, Nayyar H, Kalra S, Sharma P, Munshi A, Singh S, Kumar R (2017) Pyrimidine containing epidermal growth factor receptor kinase inhibitors: synthesis and biological evaluation. Chem Biol Drug Des 90:995–1006.  https://doi.org/10.1111/cbdd.13027 CrossRefGoogle Scholar
  20. Jousson O et al (2000) Invasive alga reaches California. Nature 408:157–158.  https://doi.org/10.1038/35041623 CrossRefGoogle Scholar
  21. Kochanowska-Karamyan AJ, Hamann MT (2010) Marine indole alkaloids: potential new drug leads for the control of depression and anxiety. Chem Rev 110:4489–4497.  https://doi.org/10.1021/cr900211p CrossRefGoogle Scholar
  22. Lakmal HC, Samarakoon KW, Lee W, Lee J-H, Abeytunga D, Lee H-S, Jeon Y-J (2014) Anticancer and antioxidant effects of selected Sri Lankan marine algae. J Natl Sci Found 42:315–323.  https://doi.org/10.4038/jnsfsr.v42i4.7730 Google Scholar
  23. Lee JC, Hou MF, Huang HW, Chang FR, Yeh CC, Tang JY, Chang HW (2013) Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties. Cancer Cell Int 13:55.  https://doi.org/10.1186/1475-2867-13-55 CrossRefGoogle Scholar
  24. Lemée R, Pesando D, Durand-Clement M, Dubreuil A, Meinesz A, Guerriero A, Pietra F (1993) Preliminary survey of toxicity of the green alga Caulerpa taxifolia introduced into the Mediterranean. J Appl Phycol 5:485–493.  https://doi.org/10.1007/BF02182507 CrossRefGoogle Scholar
  25. Marić P, Ahel M, Senta I, Terzić S, Mikac I, Žuljević A, Smital T (2017) Effect-directed analysis reveals inhibition of zebrafish uptake transporter Oatp1d1 by caulerpenyne, a major secondary metabolite from the invasive marine alga Caulerpa taxifolia. Chemosphere 174:643–654.  https://doi.org/10.1016/j.chemosphere.2017.02.007 CrossRefGoogle Scholar
  26. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. FEBS J 47:469–474.  https://doi.org/10.1111/j.1432-1033.1974.tb03714.x Google Scholar
  27. Mehdinezhad N, Ghannadi A, Yegdaneh A (2016) Phytochemical and biological evaluation of some Sargassum species from Persian gulf. Res Pharm Sci 11:243–249Google Scholar
  28. Morciano G, Giorgi C, Balestra D, Marchi S, Perrone D, Pinotti M, Pinton P (2016) Mcl-1 involvement in mitochondrial dynamics is associated with apoptotic cell death. Mol Biol Cell 27:20–34.  https://doi.org/10.1091/mbc.e15-01-0028 CrossRefGoogle Scholar
  29. Noh J, Kwon B, Han E, Park M, Yang W, Cho W, Yoo W, Khang G, Lee D (2015) Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death. Nat Commun 6:6907.  https://doi.org/10.1038/ncomms7907 CrossRefGoogle Scholar
  30. Otoguro K et al (2011) In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei. Phytochemistry 72:2024–2030.  https://doi.org/10.1016/j.phytochem.2011.07.015 CrossRefGoogle Scholar
  31. Paduch R, Kandefer-Szerszeń M, Trytek M, Fiedurek J (2007) Terpenes: substances useful in human healthcare. Arch Immunol Ther Exp 55:315.  https://doi.org/10.1007/s00005-007-0039-1 CrossRefGoogle Scholar
  32. Papini A, Mosti S, Santosuosso U (2013) Tracking the origin of the invading Caulerpa (Caulerpales, Chlorophyta) with geographic profiling, a criminological technique for a killer alga. Biol Invasions 15:1613–1621.  https://doi.org/10.1007/s10530-012-0396-5 CrossRefGoogle Scholar
  33. Pesando D, Lemée R, Ferrua C, Amade P, Girard J-P (1996) Effects of caulerpenyne, the major toxin from Caulerpa taxifolia on mechanisms related to sea urchin egg cleavage. Aquat Toxicol 35:139–155.  https://doi.org/10.1016/0166-445X(96)00013-6 CrossRefGoogle Scholar
  34. Rasul A, Bao R, Malhi M, Zhao B, Tsuji I, Li J, Li X (2013) Induction of apoptosis by costunolide in bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction. Molecules 18:1418–1433.  https://doi.org/10.3390/molecules18021418 CrossRefGoogle Scholar
  35. Roleira FM, Tavares-da-Silva EJ, Varela CL, Costa SC, Silva T, Garrido J, Borges F (2015) Plant derived and dietary phenolic antioxidants: anticancer properties. Food Chem 183:235–258.  https://doi.org/10.1016/j.foodchem.2015.03.039 CrossRefGoogle Scholar
  36. Ryu MJ, Kim AD, Khang KA, Chung HS, Kim HS, Suh IS, Chang WY, Hyun JW (2013) The green algae Ulva fasciata Delile extract induces apoptotic cell death in human colon cancer cells. In Vitro Cell Dev Biol Anim 49:74–81.  https://doi.org/10.1007/s11626-012-9547-3 CrossRefGoogle Scholar
  37. Schumacker PT (2015) Reactive oxygen species in cancer: a dance with the devil. Cancer Cell 27:156–157.  https://doi.org/10.1016/j.ccell.2015.01.007 CrossRefGoogle Scholar
  38. Tejada S, Capó X, Martorell M, Box A, Sureda A (2016) Caulerpenyne from the genus Caulerpa: biological and clinical effects. In: Environmental Research Journal, 3: 357–371.  https://doi.org/10.1038/nchembio.1712
  39. Weinberg SE, Chandel NS (2015) Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol 11:9–15.  https://doi.org/10.1038/nchembio.1712 CrossRefGoogle Scholar
  40. Yang P, Liu DQ, Liang TJ, Zhang HY, Liu AH, Guo YW, Mao SC (2015) Bioactive constituents from the green alga Caulerpa racemosa. Bioorg Med Chem 23:38–45.  https://doi.org/10.1016/j.bmc.2014.11.031 CrossRefGoogle Scholar
  41. Yeh CC, Tseng CN, Yang JI, Huang HW, Fang Y, Tang JY, Chang FR, Chang HW (2012) Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells by ethanolic extract of Gracilaria tenuistipitata. Molecules 17:10916–10927.  https://doi.org/10.3390/molecules170910916 CrossRefGoogle Scholar

Copyright information

© Slovak Academy of Sciences 2018

Authors and Affiliations

  1. 1.Advanced Technology Platform Centre, Regional Centre for BiotechnologyFaridabadIndia
  2. 2.Centre for BiosciencesCentral University of PunjabBathindaIndia
  3. 3.Department of Human Genetics and Molecular MedicineCentral University of PunjabBathindaIndia
  4. 4.Department of Plant SciencesCentral University of PunjabBathindaIndia

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