Skip to main content
SpringerLink
Log in

Marine bacterial surfactin CS30-2 induced necrosis-like cell death in Huh7.5 liver cancer cells

  • Biology
  • Published:
Journal of Oceanology and Limnology Aims and scope Submit manuscript

Abstract

Marine bacterial strain Bacillus sp. CS30 exhibited high anticancer activity against Huh7.5 human liver cancer. We purified the corresponding anticancer agent by sequential acidic precipitation, methanol extraction, Sephadex LH-20 chromatography, and reversed phase high-performance liquid chromatography (RP-HPLC), then analyzed it in mass spectrometry. Based on the results of purification and mass spectrometry, we deduced that the anticancer agent was the same component as our previously purified antifungal agent surfactin CS30-2. However, to the best of our knowledge, this is the first report on the surfactin possessing both antifungal and anticancer activities. Surfactin CS30-2 was demonstrated to exhibit high anticancer activity in a dose-dependent manner against Huh7.5 liver cancer cells. Further investigation showed that surfactin CS30-2 induced the increased generation of reactive oxygen species (ROS) and severe disruption of cell membrane, thus leading to cell death. However, unlike previously reported surfactins, surfactin CS30-2 caused cancer cell death via necrosis instead of apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Barzkar N, Tamadoni Jahromi S, Poorsaheli H B, Vianello F. 2019. Metabolites from marine microorganisms, micro, and macroalgae: immense scope for pharmacology. Mar. Drugs, 17(8): 464.

    Article  Google Scholar 

  • Cadenas E, Davies K J A. 2000. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic. Biol. Med., 29(3–4): 222–230.

    Article  Google Scholar 

  • Cao X H, Wang A H, Wang C L, Mao D Z, Lu M F, Cui Y Q, Jiao R Z. 2010. Surfactin induces apoptosis in human breast cancer MCF-7 cells through a ROS/JNK-mediated mitochondrial/caspase pathway. Chem - Biol. Interact., 183(3): 357–362.

    Article  Google Scholar 

  • Demain A L, Sanchez S. 2009. Microbial drug discovery: 80 years of progress. J. Antibiot., 62(1): 5–16.

    Article  Google Scholar 

  • Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol., 35(4): 495–516.

    Article  Google Scholar 

  • Fei F R, Hu R Y, Gong W W, Pan J, Wang M. 2019. Analysis of mortality and survival rate of liver cancer in Zhejiang Province in China: a general population-based study. Can. J. Gastroenterol. Hepatol., 2019: 1074286.

  • Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D M, Forman D, Bray F. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 136(5): E359–86.

    Article  Google Scholar 

  • Gudiña E J, Teixeira J A, Rodrigues L R. 2016. Biosurfactants produced by marine microorganisms with therapeutic applications. Mar. Drugs, 14(2): E38.

    Article  Google Scholar 

  • Hajare S N, Subramanian M, Gautam S, Sharma A. 2013. Induction of apoptosis in human cancer cells by a Bacillus lipopeptide bacillomycin D. Biochimie, 95(9): 1 722–1 731.

    Article  Google Scholar 

  • Hermawan A, Putri H. 2018. Current report of natural product development against breast cancer stem cells. Int. J. Biochem. Cell Biol., 104: 114–132.

    Article  Google Scholar 

  • Iwasaki A, Ohno O, Katsuyama S, Morita M, Sasazawa Y, Dan S, Simizu S, Yamori T, Suenaga K. 2015. Identification of a molecular target of kurahyne, an apoptosis-inducing lipopeptide from marine cyanobacterial assemblages. Bioorg. Med. Chem. Lett., 25 (22): 5 295–5 298, https://doi.org/10.1016/j.bmcl.2015.09.044.

    Google Scholar 

  • Kuang S, Liu G, Cao R B, Zhang L L, Yu Q, Sun C M. 2017. Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore. Oncotarget, 8(61): 104 057–104 071.

    Article  Google Scholar 

  • Liu G, Kuang S, Cao R B, Wang J, Peng Q C, Sun C M. 2019. Sorafenib kills liver cancer cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids via the ATP-AMPK-mTOR-SREBP1 signaling pathway. FASEB J., 33(9): 10 089–10 103.

    Article  Google Scholar 

  • ]Liu G, Wang K, Kuang S, Cao R B, Bao L, Liu R, Liu H W, Sun C M. 2018. The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism and triggering cell death. Cell Death Dis., 9(6): 689, https://doi.org/10.1038/s41419-018-0731-6.

    Article  Google Scholar 

  • Ni C H, Yu C S, Lu H F, Yang J S, Huang H Y, Chen P Y, Wu S H, Ip S W, Chiang S Y, Lin J G, Chung J G. 2014. Chrysophanol-induced cell death (Necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential. Environ. Toxicol., 29(7): 740–749.

    Article  Google Scholar 

  • Obtel M, Lyoussi B, Tachfouti N, Pelissier S M, Nejjari C. 2015. Using surveillance data to understand cancer trends: an overview in Morocco. Arch. Public Health, 73: 45.

    Article  Google Scholar 

  • Ouyang L, Shi Z, Zhao S, Wang F T, Zhou T T, Liu B, Bao J K. 2012. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif., 45(6): 487–498.

    Article  Google Scholar 

  • Park S Y, Kim J H, Lee Y J, Lee S J, Kim Y. 2013. Surfactin suppresses TPA-induced breast cancer cell invasion through the inhibition of MMP-9 expression. Int. J. Oncol., 42(1): 287–296.

    Article  Google Scholar 

  • Schinke C, Martins T, Queiroz S C N, Melo I S, Reyes F G R. 2017. Antibacterial compounds from marine bacteria, 2010–2015. J. Nat. Prod., 80(4): 1 215–1 228.

    Article  Google Scholar 

  • Sia D, Villanueva A, Friedman S L, Llovet J M. 2017. Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology, 152(4): 745–761.

    Article  Google Scholar 

  • Torre L A, Islami F, Siegel R L, Ward E M, Jemal A. 2017. Global cancer in women: burden and trends. Cancer Epidemiol. Biomarkers Prev., 26(4): 444–457.

    Article  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin M T D, Mazur M, Telser J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 39(1): 44–84.

    Article  Google Scholar 

  • Wang C L, Liu C, Niu L L, Wang L R, Hou L H, Cao X H. 2013. Surfactin-induced apoptosis through ROS-ERSCa2+-ERK pathways in HepG2 cells. Cell Biochem. Biophys., 67(3): 1 433–1 439.

    Article  Google Scholar 

  • Wu S M, Liu G, Zhou S N, Sha Z X, Sun C M. 2019. Characterization of antifungal lipopeptide biosurfactants produced by marine bacterium Bacillus sp. CS30. Mar. Drugs, 17(4): 199, https://doi.org/10.3390/md17040199.

    Article  Google Scholar 

  • Wu Y S, Ngai S C, Goh B H, Chan K G, Lee L H, Chuah L H. 2017. Anticancer activities of surfactin and potential application of nanotechnology assisted surfactin delivery. Front. Pharmacol., 8: 761, https://doi.org/10.3389/fphar.2017.00761.

    Article  Google Scholar 

  • Xiu P Y, Liu R, Zhang D C, Sun C M. 2017. Pumilacidin-like lipopeptides derived from marine bacterium Bacillus sp. Strain 176 suppress the motility of Vibrio alginolyticus. Appl. Environ. Microbiol., 83(12): e00450–17, https://doi.org/10.1128/AEM.00450-17.

    Article  Google Scholar 

  • Yang H, Li X, Li X, Yu H M, Shen Z Y. 2015. Identification of lipopeptide isoforms by MALDI-TOF-MS/MS based on the simultaneous purification of iturin, fengycin, and surfactin by RP-HPLC. Anal. Bioanal. Chem., 407(9): 2 529–2 542.

    Article  Google Scholar 

  • Zhang Y X, Yu P F, Gao Z M, Yuan J, Zhang Z. 2017. Caffeic acid n-butyl ester-triggered necrosis-like cell death in lung cancer cell line A549 is prompted by ROS mediated alterations in mitochondrial membrane potential. Eur. Rev. Med. Pharmacol. Sci., 21(7): 1 665–1 671.

    Google Scholar 

  • Zhao H B, Shao D Y, Jiang C M, Shi J L, Li Q, Huang Q S, Rajoka M S R, Yang H, Jin M L. 2017. Biological activity of lipopeptides from Bacillus. Appl. Microbiol. Biotechnol., 101(15): 5 951–5 960, https://doi.org/10.1007/s00253-017-8396-0.

    Article  Google Scholar 

  • Zhong H Q, Xiao M Q, Zarkovic K, Zhu M J, Sa R N, Lu J H, Tao Y Z, Chen Q, Xia L, Cheng S Q, Waeg G, Zarkovic N, Yin H Y. 2017. Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: a novel link between oxidative stress and cancer. Free Radical Biol. Med., 102: 67–76, https://doi.org/10.1016/j.freeradbiomed.2016.10.494.

    Article  Google Scholar 

  • Zong W X, Ditsworth D, Bauer D E, Wang Z Q, Thompson C B. 2004. Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev., 18(11): 1 272–1 282.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Life Sciences, Qingdao University, Qingdao, 266071, China

    Shengnan Zhou & Shimei Wu

  2. Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China

    Ge Liu

  3. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China

    Ge Liu

Authors
  1. Shengnan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ge Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shimei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shimei Wu.

Additional information

Supported by the National Natural Science Foundation of China (No. 31600035) to WU Shimei

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, S., Liu, G. & Wu, S. Marine bacterial surfactin CS30-2 induced necrosis-like cell death in Huh7.5 liver cancer cells. J. Ocean. Limnol. 38, 826–833 (2020). https://doi.org/10.1007/s00343-019-9129-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00343-019-9129-2

Keyword

Search

Navigation