In vitro anti-cancer potency of Mortierella elongata lipids against MCF 7 cells through induction of apoptosis and cell cycle arrest

S. Ida Poornima V. Judia Harriet Sumathy   

Open Access   

Published:  May 03, 2024

DOI: 10.7324/JABB.2024.164058
Abstract

Globally, cancer remains the second-whacking cause of mortality. Several studies, like in vitro cell studies, clinical trials, in vivo studies, and cohort studies, have authenticated the anticancer potency of omega-3 polyunsaturated fatty acids (PUFA) against various cancer types. The present study reports the in vitro anticancer potency of PUFA produced by Mortierella elongata (Accession No. OK402027) against Michigan Cancer Foundation-7 (MCF-7) breast cancer cell lines. The biocompatibility and cytotoxicity of M. elongata lipids were evaluated against human embryonic kidney and MCF-7 cells, respectively. The anti-proliferative activity of M. elongata lipids was examined at three different concentrations based on the inhibitory concentration (IC50) value. The apoptotic activity of M. elongata lipids was analyzed by fluorescence microscopy by implementing three different staining methods, such as acridine orange/ethidium bromide, 4,6-diamidino-2-phenylindole, and propidium iodide. Further, the biological activity of M. elongata on apoptosis induction, cell cycle progression, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation were evaluated. The MTT assay revealed the anti-proliferative activity of M. elongata lipids, and the IC50 value of M. elongata lipids at 24 h was found to be 28 ± 1.3 μg/mL. A significant decrease in the percentage of live cells with 57.36% of apoptotic and 14.10% of necrotic cells was revealed in cells treated with 100 μg/mL of M. elongata lipids. Anti-proliferative activity is associated with increased ROS generation and the loss of MMP. The lipids of M. elongata induced a dose-dependent G1 arrest and were found to be more effective at 100 μg/ml, accumulating 54.49% of MCF-7 cells in the G1 phase. Taken together, the present study has confirmed the in vitro anticancer potency of M. elongata lipids via apoptosis and cell cycle arrest.


Keyword:     Polyunsaturated fatty acids Omega 3 Omega 6 Oleaginous fungi Anticancer


Citation:

Poornima SI, Sumathy VJH. In vitro anti-cancer potency of Mortierella elongata lipids against MCF 7 cells through induction of apoptosis and cell cycle arrest. J App Biol Biotech. 2024. Online First. http://doi.org/10.7324/JABB.2024.164058

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

HTML Full Text
Reference

1. Brown I, Cascio MG, Rotondo D, Pertwee RG, Heys SD, Wahle KW. Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. Prog Lipid Res 2013;52:80-109. https://doi.org/10.1016/j.plipres.2012.10.001

2. Rovito D, Giordano C, Vizza D, Plastina P, Barone I, Casaburi I, et al. Omega?3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARγ activation in MCF?7 breast cancer cells. J Cell Physiol 2013;228:1314-22. https://doi.org/10.1002/jcp.24288

3. Brown I, Cascio MG, Wahle KW, Smoum R, Mechoulam R, Ross RA, et al. Cannabinoid receptor-dependent and-independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and-negative prostate cancer cell lines. Carcinogenesis 2010;31:1584-91. https://doi.org/10.1093/carcin/bgq151

4. Brown I, Lee J, Sneddon AA, Cascio MG, Pertwee RG, Wahle KW, et al. Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion. Prostaglandins Leukot Essent Fatty Acids 2020;156:102024. https://doi.org/10.1016/j.plefa.2019.102024

5. Mansara P, Ketkar M, Deshpande R, Chaudhary A, Shinde K, Kaul-Ghanekar R. Improved antioxidant status by omega-3 fatty acid supplementation in breast cancer patients undergoing chemotherapy: A case series. J Med Case Rep 2015;9:148. https://doi.org/10.1186/s13256-015-0619-3

6. Thangam R, Suresh V, Rajkumar M, Vincent JD, Gunasekaran P, Anbazhagan C, et al. Antioxidant and in vitro anticancer effect of 2?pyrrolidinone rich fraction of Brassica oleracea var. capitata through induction of apoptosis in human cancer cells. Phytother Res 2013;27:1664-70. https://doi.org/10.1002/ptr.4908

7. Saengkhae C, Premsuriya Y, Srivibool R, Praiboon J. Sensitization of human carcinoma of nasopharynx cells to doxorubicin and induction of apoptosis by Sargassum baccularia lipophilic fraction. Walailak J Sci Technol 2015;12:515-25.

8. Al-Assaf AH. Chemopreventive effect of corosolic acid in human hepatocellular carcinoma cells. Afr J Biotechnol 2013;12:2733-42.

9. Sivandzade F, Bhalerao A, Cucullo L. Analysis of the mitochondrial membrane potential using the cationic JC-1 dye as a sensitive fluorescent probe. Bio Protoc 2019;9:e3128. https://doi.org/10.21769/BioProtoc.3128

10. Cheng MH, Walker TH, Hulbert GJ, Raman DR. Fungal production of eicosapentaenoic and arachidonic acids from industrial waste streams and crude soybean oil. Bioresour Technol 1999;67:101-10. https://doi.org/10.1016/S0960-8524(98)00113-8

11. Stredansky M, Conti E, Salaris A. Production of polyunsaturated fatty acids by Pythium ultimum in solid-state cultivation. Enzyme Microb Technol 2020;26:304-7. https://doi.org/10.1016/S0141-0229(99)00146-5

12. Deshpande S, Patil T, Alone S, Duragkar N. Microbial conversion of plant based polyunsaturated fatty acid (PUFA) to long chain pufa and its identification by gas chromatography. J Biotechnol Biomater 2013;S13:6. https://doi.org/10.4172/2155-952X.S13-006

13. Das UN. Tumoricidal action of cis-unsaturated fatty acids and their relationship to free radicals and lipid peroxidation. Cancer Lett 1991;56:235-43. https://doi.org/10.1016/0304-3835(91)90008-6

14. Sagar PS, Das UN. Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma (HeLa) cells in vitro. Prostaglandins Leukot Essent Fatty Acids 1995;53:287-99. https://doi.org/10.1016/0952-3278(95)90129-9

15. Ramesh G, Das UN. Effect of cis-unsaturated fatty acids on Meth-A ascitic tumour cells in vitro and in vivo. Cancer Lett 1998;123:207-14. https://doi.org/10.1016/S0304-3835(97)00426-6

16. Das UN, Madhavi N. Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro. Lipids Health Dis 2011;10:159. https://doi.org/10.1186/1476-511X-10-159

17. Dai J, Shen J, Pan W, Shen S, Das UN. Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro. Lipids Health Dis 2013;12:71. https://doi.org/10.1186/1476-511X-12-71

18. Meng H, Liu Y, Zhai Y, Lai L. Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase. Eur J Med Chem 2013;59:160-7. https://doi.org/10.1016/j.ejmech.2012.10.057

19. Sayegh F, Elazzazy A, Bellou S, Moustogianni A, Elkady AI, Baeshen MN, et al. Production of polyunsaturated single cell oils possessing antimicrobial and anticancer properties. Ann Microbiol 2016;66:937-48. https://doi.org/10.1007/s13213-015-1176-0

20. Baldeweg F, Warncke P, Fischer D, Gressler M. Fungal biosurfactants from Mortierella alpina. Org Lett 2019;21:1444-8. https://doi.org/10.1021/acs.orglett.9b00193

21. Abu-Elghait M, Hasanin M, Hashem AH, Salem SS. Ecofriendly novel synthesis of tertiary composite based on cellulose and myco-synthesized selenium nanoparticles: Characterization, antibiofilm and biocompatibility. Int J Biol Macromol 2021;175:294-303. https://doi.org/10.1016/j.ijbiomac.2021.02.040

22. European Food Safety Authority (EFSA). Safety of 'fungal oil from Mortierella alpina'?scientific opinion of the panel on dietetic products, nutrition and allergies. EFSA J 2008;6:770. https://doi.org/10.2903/j.efsa.2008.770

23. Al?Hwaiti MS, Alsbou EM, Abu Sheikha G, Bakchiche B, Pham TH, Thomas RH, et al. Evaluation of the anticancer activity and fatty acids composition of "Handal"(Citrullus colocynthis L.) seed oil, a desert plant from south Jordan. Food Sci Nutr 2021;9:282-9. https://doi.org/10.1002/fsn3.1994

24. Vilakazi H, Olasehinde TA, Olaniran AO. Chemical characterization, antiproliferative and antioxidant activities of polyunsaturated fatty acid-rich extracts from Chlorella sp. S14. Molecules 2021;26:4109. https://doi.org/10.3390/molecules26144109

25. Palakurthi SS, Flu?ckiger R, Aktas H, Changolkar AK, Shahsafaei A, Harneit S, et al. Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Res 2000;60:2919-25.

26. So WW, Liu WN, Leung KN. Omega-3 polyunsaturated fatty acids trigger cell cycle arrest and induce apoptosis in human neuroblastoma LA-N-1 cells. Nutrients 2015;7:6956-73. https://doi.org/10.3390/nu7085319

27. Chatterjee N, Das S, Bose D, Banerjee S, Jha T, Das Saha K. Lipid from infective L. donovani regulates acute myeloid cell growth via mitochondria dependent MAPK pathway. PLoS One 2015;10:e0120509. https://doi.org/10.1371/journal.pone.0120509

28. Roy S, Rawat AK, Sammi SR, Devi U, Singh M, Gautam S, et al. Alpha-linolenic acid stabilizes HIF-1 α and downregulates FASN to promote mitochondrial apoptosis for mammary gland chemoprevention. Oncotarget 2017;8:70049. https://doi.org/10.18632/oncotarget.19551

29. Giulitti F, Petrungaro S, Mandatori S, Tomaipitinca L, De Franchis V, D'Amore A, et al. Anti-tumor effect of oleic acid in hepatocellular carcinoma cell lines via autophagy reduction. Front Cell Dev Biol 2021;9:629182. https://doi.org/10.3389/fcell.2021.629182

30. Iuchi K, Ema M, Suzuki M, Yokoyama C, Hisatomi H. Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells. Mol Med Rep 2019;19:2767-73. https://doi.org/10.3892/mmr.2019.9940

31. Gbayisomore O, Klausner H, Phelan SA. Punicic acid inhibits proliferation and induces apoptosis in human MCF-7 breast cancer cells. Int J Cancer Clin Res 2023;10:179. https://doi.org/10.23937/2378-3419/1410179

32. Avula CR, Zaman AK, Lawrence R, Fernandes G. Induction of apoptosis and apoptotic mediators in balb/C splenic lymphocytes by dietary n- 3 and n- 6 fatty acids. Lipids 1999;34:921-7. https://doi.org/10.1007/s11745-999-0441-1

33. Wang CC, Liu WB, Cao XF, Huang YY, Wang X, Xiao K, et al. Excess DHA induces cell cycle arrest by activating the P53/cycling pathway in blunt snout bream (Megalobrama amblycephala). Front Mar Sci 2020;7:286. https://doi.org/10.3389/fmars.2020.00286

34. D'Eliseo D, Velotti F. Omega-3 fatty acids and cancer cell cytotoxicity: Implications for multi-targeted cancer therapy. J Clin Med 2016;5:15. https://doi.org/10.3390/jcm5020015

35. Oono K, Ohtake K, Watanabe C, Shiba S, Sekiya T, Kasono K. Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells. Lipids Health Dis 2020;19:15. https://doi.org/10.1186/s12944-019-1122-4

Article Metrics
23 Views 3 Downloads 26 Total

Year

Month

Related Search

By author names