Study of mTOR/PTEN gene expression in gastric cancer cell line treated with ethanolic extract of Tetraselmis suecia microalgae

Atena Ehsanbakhsh; Narges Javadzadeh

doi:10.22034/ijab.v13i4.2573

Authors

Atena Ehsanbakhsh Department of Biotechnology, Ahv.C., Islamic Azad University, Ahvaz, Iran.
Narges Javadzadeh
Nargesjavadzadeh@iau.ac.ir
Department of Fisheries, Ahv.C., Islamic Azad University, Ahvaz, Iran.

Vol. 13 No. 4 (2025): August

Articles

August 14, 2025

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The second leading cause of death worldwide is cancer, and the fourth most prevalent cancer is stomach cancer. Natural seafood products include a variety of biologically active compounds with medicinal properties that may be useful in cancer therapy. This study aimed to assess the growth-inhibitory impact of the ethanolic extract of Tetraselmis suecica algae on the expression of mTOR/PTEN genes using the MTT assay in the cell line. The optimal IC50 dosage of this extract was 1000 and 750 ?g/mL at 48 and 72 hours, respectively. Tetraselmis suecica extract dramatically lowered the survival rate of gastric cancer cells, increased the apoptotic PTEN gene expression, and decreased the mTOR gene expression in the cell line. The extract of T. suecica, as shown in the current study, is potentially useful in the treatment of stomach cancer.

Ehsanbakhsh, A., & Javadzadeh, N. (2025). Study of mTOR/PTEN gene expression in gastric cancer cell line treated with ethanolic extract of Tetraselmis suecia microalgae. International Journal of Aquatic Biology, 13(4), 10–17. https://doi.org/10.22034/ijab.v13i4.2573

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Ahmad I., Hoque M., Alam S.S.M., Zughaibi T.A., Tabrez S. (2023). Curcumin and plumbagin synergistically target the PI3K/Akt/mTOR pathway: a prospective role in cancer treatment. International Journal of Molecular Sciences, 24(7): 6651.

Ashrafizadeh M., Zarrabi A., Hushmandi K., Kalantari M., Mohammadinejad R., Javaheri T., Sethi G. (2020). Association of the epithelial–mesenchymal transition (EMT) with cisplatin resistance. International Journal of Molecular Sciences, 21(11): 4002.

Asoudeh-Fard A., Sis F.F., Rahmani B., Kamranjam M., Soltanmohammadi F., Jahromi M.Z., Parsai A. (2025). Inhibitory effects of Tetraselmis algae extract on cervical cancer cell proliferation: a molecular and cellular approach. Molecular Biology Reports, 52(1): 473.

Bergholz J.S., Wang Q., Wang Q., Ramseier M., Prakadan S., Wang W., Fang R., Kabraji S., Zhou Q., Gray G.K. (2023). PI3K? controls immune evasion in PTEN-deficient breast tumours. Nature, 617(7959): 139-146.

Cheragh M.R., Mabudi H. (2023). Effect of Tetraselmis suecica microalgae isolated from the Persian Gulf on the expression level of AKT/mTOR genes in the liver cancer cell line, Huh7. International Journal of Aquatic Biology, 11(6): 563-570.

Chu W.-L., Phang S.-M. (2020). Bioactive compounds from microalgae and their potential applications as pharmaceuticals and nutraceuticals. In: Grand challenges in algae biotechnology. pp: 429-469.

Davoodi N., Mabudi H., (2024). The effect of the ethanolic extract of Tetraselmis suecica microalgae isolated from the Persian Gulf on the expression of BAX/BCL-2 genes in the HeLa cervical cancer cell line. International Journal of Aquatic Biology, 12(5): 495-502.

Dillon R., White D., Muller W. (2007). The phosphatidyl inositol 3-kinase signaling network: Implications for human breast cancer. Oncogene, 26(9): 1338-1345.

Fang W.-L., Huang K.-H., Lan Y.-T., Lin C.-H., Chang S.-C., Chen M.-H., Chao Y., Lin W.-C., Lo S.-S., Li A.F.-Y. (2015). Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers. Oncotarget, 7(5): 6201.

Feldman D.R., Iyer G., Van Alstine L., Patil S., Al-Ahmadie H., Reuter V.E., Bosl G.J., Chaganti R.S., Solit D.B. (2014). Presence of somatic mutations within PIK3CA, AKT, RAS, and FGFR3 but not BRAF in cisplatin-resistant germ cell tumors. Clinical Cancer Research, 20(14): 3712-3720.

Fusco N., Sajjadi E., Venetis K., Gaudioso G., Lopez G., Corti C., Rocco E.G., Criscitiello C., Malapelle U., Invernizzi M. (2020). PTEN alterations and their role in cancer management: Are we making headway on precision medicine? Genes, 11(7): 719.

Glaviano A., Foo A.S., Lam H.Y., Yap K.C., Jacot W., Jones R.H., Eng H., Nair M.G., Makvandi P., Geoerger B. (2023). PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Molecular Cancer, 22(1): 138.

Hennessy B.T., Smith D.L., Ram P.T., Lu Y., Mills G.B. (2005). Exploiting the PI3K/AKT pathway for cancer drug discovery. Nature Reviews Drug Discovery, 4(12): 988-1004.

Hsieh S.-M., Maguire D., Lintell N., McCabe M., Griffiths L. (2007). PTEN and NDUFB8 aberrations in cervical cancer tissue. Oxygen Transport to Tissue XXVIII, Springer: 31-36.

Hussein H.A., Mohamad H., Ghazaly M.M., Laith A., Abdullah M.A. (2020). Cytotoxic effects of Tetraselmis suecica chloroform extracts with silver nanoparticle co-application on MCF-7, 4 T1, and Vero cell lines. Journal of Applied Phycology, 32: 127-143.

Jiang N., Dai Q., Su X., Fu J., Feng X., Peng J. (2020). Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Molecular Biology Reports, 47(6): 4587-4629.

Jin J., Shi Y., Zhang S., Yang S. (2020). PIK3CA mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis. Acta Oncologica, 59(1): 66-74.

Khan M.I., Shin J.H., Kim J.D. (2018). The promising future of microalgae: current status, challenges, and optimization of a sustainable and renewable industry for biofuels, feed, and other products. Microbial Cell Factories, 17: 1-21.

Ko J.H., Um J.Y., Lee S.G., Yang W.M., Sethi G., Ahn K.S. (2019). Conditioned media from adipocytes promote proliferation, migration, and invasion in melanoma and colorectal cancer cells. Journal of Cellular Physiology, 234(10): 18249-18261.

Kucerova P., Cervinkova M. (2016). Spontaneous regression of tumour and the role of microbial infection–possibilities for cancer treatment. Anti-Cancer Drugs 27(4): 269-277.

Landa I., Ibrahimpasic T., Boucai L., Sinha R., Knauf J.A., Shah R.H., Dogan S., Ricarte-Filho J.C., Krishnamoorthy G.P., Xu B. (2016). Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. The Journal of Clinical Investigation, 126(3): 1052-1066.

Lee J., Kim Y., Lee M., Park C., Min K. (2003). Expression of PTEN in renal cell carcinoma and the relation to tumor growth and behavior. Laboratory Investigation, Lippincott Williams and Wilkins 530 Walnut St, Philadelphia, PA 19106-3621 USA.

Leung A., Rangamani P. (2023). Computational modeling of AMPK and mTOR crosstalk in glutamatergic synapse calcium signaling. NPJ Systems Biology and Applications, 9(1): 34.

Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie L. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275(5308): 1943-1947.

Li M., Liu F., Zhang F., Zhou W., Jiang X., Yang Y., Qu K., Wang Y., Ma Q., Wang T. (2019). Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis. Gut, 68(6): 1024-1033.

Li Q., Bai Y., Lyle L.T., Yu G., Amarasinghe O., Nguele Meke F., Carlock C., Zhang Z.-Y. (2020). Mechanism of PRL2 phosphatase-mediated PTEN degradation and tumorigenesis. Proceedings of the National Academy of Sciences, 117(34): 20538-20548.

Manning B.D., Cantley L.C. (2007). AKT/PKB signaling: Navigating downstream. Cell, 129(7): 1261-1274.

Marafie S.K., Al-Mulla F., Abubaker J. (2024). mTOR: Its critical role in metabolic diseases, cancer, and the aging process. International Journal of Molecular Sciences, 25(11): 6141.

Martínez K.A., Saide A., Crespo G., Martín J., Romano G., Reyes F., Lauritano C., Ianora A. (2022). Promising antiproliferative compound from the green microalga Dunaliella tertiolecta against human cancer cells. Frontiers in Marine Science, 9: 778108.

Masoumi S., Zokaei M., Ahmadvand A., Ghalamkarpour N., Asadimanesh N., Azarimatin A., Fattah K., Payandeh K., Rostami M., Farjami A. (2025). Microalgae: A treasure trove of anticancer nutraceuticals and promising therapeutic mechanisms. Advanced Biomedical Research, 1: 5.

Miller T.W., Pérez-Torres M., Narasanna A., Guix M., Sta?l O., Pérez-Tenorio G., Gonzalez-Angulo A.M., Hennessy B.T., Mills G.B., Kennedy J.P. (2009). Loss of phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer. Cancer Research, 69(10): 4192-4201.

Ooki A., Yamashita K., Kikuchi S., Sakuramoto S., Katada N., Waraya M., Kawamata H., Nishimiya H., Nakamura K., Watanabe M. (2011). Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer. BMC Cancer, 11: 1-11.

Parra-Riofrío G., García-Márquez J., Casas-Arrojo V., Uribe-Tapia E., Abdala-Díaz R.T. (2020). Antioxidant and cytotoxic effects on tumor cells of exopolysaccharides from Tetraselmis suecica (Kylin) butcher grown under autotrophic and heterotrophic conditions. Marine Drugs, 18(11): 534.

Pérez-Ramírez C., Cañadas-Garre M., Molina M.Á., Faus-Dáder M.J., Calleja-Hernández M.Á. (2015). PTEN and PI3K/AKT in non-small-cell lung cancer. Pharmacogenomics, 16(16): 1843-1862.

Prabakaran G., Moovendhan M., Arumugam A., Matharasi A., Dineshkumar R., Sampathkumar P. (2018). Quantitative analysis of phytochemical profile in marine microalgae Chlorella vulgaris. International Journal of Pharma and Bio Sciences, 8(2): 562-565.

Puzio-Kuter A.M., Castillo-Martin M., Kinkade C., Wang X., Shen T.H., Matos T., Shen M.M., Cordon-Cardo C., Abate-Shen C. (2009). Inactivation of p53 and Pten promotes invasive bladder cancer. Genes and development, 23(6): 675-680.

Sah B.-R., Owczarczyk K., Siddique M., Cook G.J., Goh V. (2019). Radiomics in esophageal and gastric cancer. Abdominal Radiology, 44: 2048-2058.

Sidorov M., Dighe P., Woo R.W., Rodriguez B.A., Chen M., Ice R.J. Vaquero E., Jian D., Desprez P.-Y., Nosrati M. (2023). Dual targeting of EGFR and MTOR pathways inhibits glioblastoma growth by modulating the tumor microenvironment. Cells, 12(4): 547.

Song M.S., Salmena L., Pandolfi P.P. (2012). The functions and regulation of the PTEN tumour suppressor. Nature Reviews Molecular Cell Biology, 13(5): 283-296.

Tian L.-Y., Smit D.J., Jücker M. (2023). The role of PI3K/AKT/mTOR signaling in hepatocellular carcinoma metabolism. International Journal of Molecular Sciences, 24(3): 2652.

Verhaak R.G., Hoadley K.A., Purdom E., Wang V., Qi Y., Wilkerson M.D., Miller C.R., Ding L., Golub T., Mesirov J.P. (2010). Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 17(1): 98-110.

Vidotto T., Melo C., Lautert-Dutra W., Chaves L., Reis R., Squire J. (2023). Pan-cancer genomic analysis shows hemizygous PTEN loss tumors are associated with immune evasion and poor outcome. Scientific Reports, 13(1): 5049.

Vivanco I., Sawyers C.L. (2002). The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nature Reviews Cancer, 2(7): 489-501.

Yan X., Huang S., Li H., Feng Z., Kong J., Liu J. (2024). The causal effect of mTORC1-dependent circulating protein levels on nonalcoholic fatty liver disease: A Mendelian randomization study. Digestive and Liver Disease, 56(4): 559-564.

Yu L., Wei J., Liu P. (2022). Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Seminars in Cancer Biology, Elsevier.

Zhou Y.-A., Zhang T., Zhao J.-B., Wang X.-P., Jiang T., Gu Z.-P., Wang X.-N., Li X.-F. (2010). The adenovirus-mediated transfer of PTEN inhibits the growth of esophageal cancer cells in vitro and in vivo. Bioscience, Biotechnology, and Biochemistry, 74(4): 736-740.

Zhu W., Shao Y., Yang M., Jia M., Peng Y. (2016). Asparaginyl endopeptidase promotes proliferation and invasiveness of prostate cancer cells via PI3K/AKT signaling pathway. Gene, 594(2): 176-182.