Anti‑angiogenic effect of <em>Bryopsis plumosa</em>‑derived peptide via aquaporin 3 in non‑small cell lung cancer

Kim,Heabin; Jung,Seung-Hyun; Jo,Seonmi; Han,Jong Won; Yoon,Moongeun; Lee,Jei Ha

doi:10.3892/ijo.2024.5711

Anti‑angiogenic effect of Bryopsis plumosa‑derived peptide via aquaporin 3 in non‑small cell lung cancer

Authors:
- Heabin Kim
- Seung-Hyun Jung
- Seonmi Jo
- Jong Won Han
- Moongeun Yoon
- Jei Ha Lee
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Affiliations: Department of Bio‑material Research, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea, Department of Biological Application & Technology, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea, Department of Ecology & Conservation, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea
Published online on: November 27, 2024 https://doi.org/10.3892/ijo.2024.5711
Article Number: 5
Copyright : © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Developing novel anti‑angiogenic agents with minimal toxicity is notably challenging for cancer therapeutics. The discovery and development of peptides, whether derived from natural sources or synthesized, has potential for developing anti‑angiogenic agents characterized by their ability to penetrate cancer cells, high specificity and low toxicity. The present study identified a Bryopsis plumose‑derived anticancer and anti‑angiogenesis marine‑derived peptide 06 (MP06). A 22‑amino acid peptide was synthesized and conjugated with fluorescein isothiocyanate (FITC‑MP06) for intracellular localization in H1299 non‑small cell lung cancer cells. Regulatory effects of this peptide on the viability, migration and self‑renewal of lung cancer cells was assessed. Furthermore, anti‑angiogenic effect of MP06 was investigated by monitoring vascular tube formation in human umbilical vein endothelial cells and a zebrafish model. Aquaporin (AQP)3, a membrane channel in various tissues, is involved in regulating stemness, epithelial‑mesenchymal transition (EMT) and angiogenesis. MP06 downregulated AQP3 expression. Consistently, AQP3 knockdown by RNA silencing downregulated its gene expression, leading to a decrease in stemness, EMT and angiogenesis properties in H1299 cells. MP06 could thus serve as a novel therapeutic target with anticancer and angiogenesis properties for non‑small cell lung cancer.

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1	Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024. View Article : Google Scholar : PubMed/NCBI
2	Evans M: Lung cancer: Needs assessment, treatment and therapies. Br J Nurs. 22(Suppl 17): S15–S22. 2013. View Article : Google Scholar : PubMed/NCBI
3	Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL and Paz-Ares L: Lung cancer: Current therapies and new targeted treatments. Lancet. 389:299–311. 2017. View Article : Google Scholar
4	Hirsch FR, Suda K, Wiens J and Bunn PA Jr: New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 388:1012–1024. 2016. View Article : Google Scholar : PubMed/NCBI
5	Lu W and Kang Y: Epithelial-mesenchymal plasticity in cancer progression and metastasis. Dev Cell. 49:361–374. 2019. View Article : Google Scholar : PubMed/NCBI
6	Tsoukalas N, Aravantinou-Fatorou E, Tolia M, Giaginis C, Galanopoulos M, Kiakou M, Kostakis ID, Dana E, Vamvakaris I, Korogiannos A, et al: Epithelial-mesenchymal transition in non-small-cell lung cancer. Anticancer Res. 37:1773–1778. 2017. View Article : Google Scholar : PubMed/NCBI
7	Majeed U, Manochakian R, Zhao Y and Lou Y: Targeted therapy in advanced non-small cell lung cancer: Current advances and future trends. J Hematol Oncol. 14:1082021. View Article : Google Scholar : PubMed/NCBI
8	Brock CS and Lee S: Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer. Eur Resp J. 19:557–570. 2002. View Article : Google Scholar
9	Tian W, Cao C, Shu L and Wu F: Anti-angiogenic therapy in the treatment of non-small cell lung cancer. Onco Targets Ther. 13:12113–12129. 2020. View Article : Google Scholar : PubMed/NCBI
10	Yu Z, Pestell TG, Lisanti MP and Pestell RG: Cancer stem cells. Int J Biochem Cell Biol. 44:2144–2151. 2012. View Article : Google Scholar : PubMed/NCBI
11	Prabavathy D, Swarnalatha Y and Ramadoss N: Lung cancer stem cells-origin, characteristics and therapy. Stem Cell Investig. 5:62018. View Article : Google Scholar : PubMed/NCBI
12	Leon G, MacDonagh L, Finn SP, Cuffe S and Barr MP: Cancer stem cells in drug resistant lung cancer: Targeting cell surface markers and signaling pathways. Pharmacol Ther. 158:71–90. 2016. View Article : Google Scholar
13	Codony-Servat J, Verlicchi A and Rosell R: Cancer stem cells in small cell lung cancer. Transl Lung Cancer Res. 5:16–25. 2016.PubMed/NCBI
14	Shibue T and Weinberg RA: EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol. 14:611–629. 2017. View Article : Google Scholar : PubMed/NCBI
15	Krebs AM, Mitschke J, Losada ML, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, et al: The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 19:518–529. 2017. View Article : Google Scholar : PubMed/NCBI
16	Loret N, Denys H, Tummers P and Berx G: The role of epithelial-to-mesenchymal plasticity in ovarian cancer progression and therapy resistance. Cancers (Basel). 11:8382019. View Article : Google Scholar : PubMed/NCBI
17	Tanabe S, Quader S, Cabral H and Ono R: Interplay of EMT and CSC in cancer and the potential therapeutic strategies. Front Pharmacol. 11:9042020. View Article : Google Scholar : PubMed/NCBI
18	Kim H, Kim HT, Jung SH, Han JW, Jo S, Kim IG, Kim RK, Kahm YJ, Choi TI, Kim CH and Lee JH: A novel anticancer peptide derived from bryopsis plumosa regulates proliferation and invasion in non-small cell lung cancer cells. Mar Drugs. 21:6072023. View Article : Google Scholar : PubMed/NCBI
19	Rosca EV, Koskimaki JE, Rivera CG, Pandey NB, Tamiz AP and Popel AS: Anti-angiogenic peptides for cancer therapeutics. Curr Pharm Biotechnol. 12:1101–1116. 2011. View Article : Google Scholar : PubMed/NCBI
20	Karagiannis ED and Popel AS: A systematic methodology for proteome-wide identification of peptides inhibiting the proliferation and migration of endothelial cells. Proc Natl Acad Sci USA. 105:13775–13780. 2008. View Article : Google Scholar : PubMed/NCBI
21	Koskimaki JE, Karagiannis ED, Rosca EV, Vesuna F, Winnard PT Jr, Raman V, Bhujwalla ZM and Popel AS: Peptides derived from type IV collagen, CXC chemokines, and thrombospondin-1 domain-containing proteins inhibit neovascularization and suppress tumor growth in MDA-MB-231 breast cancer xenografts. Neoplasia. 11:1285–1291. 2009. View Article : Google Scholar : PubMed/NCBI
22	Ishimoto S, Wada K, Usami Y, Tanaka N, Aikawa T, Okura M, Nakajima A, Kogo M and Kamisaki Y: Differential expression of aquaporin 5 and aquaporin 3 in squamous cell carcinoma and adenoid cystic carcinoma. Int J Oncol. 41:67–75. 2012.PubMed/NCBI
23	Agre P: Aquaporin water channels. Biosci Rep. 24:127–163. 2004. View Article : Google Scholar
24	Delporte C: Aquaporins and gland secretion. Aquaporins. 969:63–79. 2017. View Article : Google Scholar
25	Papadopoulos MC and Saadoun S: Key roles of aquaporins in tumor biology. Biochim Biophys Acta. 1848:2576–2583. 2015. View Article : Google Scholar
26	Ismail M, Bokaee S, Morgan R, Davies J, Harrington KJ and Pandha H: Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy. Br J Cancer. 100:1889–1895. 2009. View Article : Google Scholar : PubMed/NCBI
27	Liu YL, Matsuzaki T, Nakazawa T, Murata SI, Nakamura N, Kondo T, Iwashina M, Mochizuki K, Yamane T, Takata K and Katoh R: Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. Hum Pathol. 38:171–178. 2007. View Article : Google Scholar
28	Li B, Jin L, Zhong K and Du D: Correlation of aquaporin 3 expression with the clinicopathologic characteristics of non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 15:404–408. 2012.In Chinese. PubMed/NCBI
29	Xia H, Ma YF, Yu CH, Li YJ, Tang J, Li JB, Zhao YN and Liu Y: Aquaporin 3 knockdown suppresses tumour growth and angiogenesis in experimental non-small cell lung cancer. Exp Physiol. 99:974–984. 2014. View Article : Google Scholar
30	Jaskiewicz L, Hejne K, Szostak B, Osowiecka K, Skowronski MT, Lepiarczyk E, Doboszynska A, Majewska M, Kordowitzki P and Skowronska A: Expression profiles of AQP3 and AQP4 in lung adenocarcinoma samples generated via Bronchoscopic biopsies. J Clin Med. 11:59542022. View Article : Google Scholar :
31	Nusslein-Volhard C and Dahm R: Zebrafish: A Practical Approach. Oxford University Press; New York, NY: 2002, View Article : Google Scholar
32	Khater I and Nassar A: Potential antiviral peptides targeting the SARS-CoV-2 spike protein. BMC Pharmacol Toxicol. 23:912022. View Article : Google Scholar : PubMed/NCBI
33	Hadianamrei R, Tomeh MA, Brown S, Wang J and Zhao X: Rationally designed short cationic α-helical peptides with selective anticancer activity. J Colloid Interface Sci. 607:488–501. 2022. View Article : Google Scholar
34	Huang YB, He LY, Jiang HY and Chen YX: Role of helicity on the anticancer mechanism of action of cationic-helical peptides. Int J Mol Sci. 13:6849–6862. 2012. View Article : Google Scholar : PubMed/NCBI
35	Lee S, Wottrich S and Bonavida B: Crosstalks between Raf-kinase inhibitor protein and cancer stem cell transcription factors (Oct4, KLF4, Sox2, Nanog). Tumor Biol. 39:10104283176922532017. View Article : Google Scholar
36	van Schaijik B, Davis PF, Wickremesekera AC, Tan ST and Itinteang T: Subcellular localisation of the stem cell markers OCT4, SOX2, NANOG, KLF4 and c-MYC in cancer: A review. J Clin Pathol. 71:88–91. 2018. View Article : Google Scholar
37	Fantozzi A, Gruber DC, Pisarsky L, Heck C, Kunita A, Yilmaz M, Meyer-Schaller N, Cornille K, Hopfer U, Bentires-Alj M and Christofori G: VEGF-mediated angiogenesis links EMT-induced cancer stemness to tumor initiation. Cancer Res. 74:1566–1575. 2014. View Article : Google Scholar : PubMed/NCBI
38	Hilchie A, Hoskin D and Coombs MR: Anticancer activities of natural and synthetic peptides. Adv Exp Med Biol. 1117:131–147. 2019. View Article : Google Scholar : PubMed/NCBI
39	Shin MK, Jang BY, Bu KB, Lee SH, Han DH, Oh JW and Sung JS: De novo design of AC-P19M, a novel anticancer peptide with apoptotic effects on lung cancer cells and anti-angiogenic activity. Int J Mol Sci. 23:155942022. View Article : Google Scholar : PubMed/NCBI
40	Chinnadurai RK, Khan N, Meghwanshi GK, Ponne S, Althobiti M and Kumar R: Current research status of anti-cancer peptides: Mechanism of action, production, and clinical applications. Biomed Pharmacother. 164:1149962023. View Article : Google Scholar : PubMed/NCBI
41	Plaks V, Kong N and Werb Z: The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 16:225–238. 2015. View Article : Google Scholar : PubMed/NCBI
42	Iliopoulos D, Hirsch HA and Struhl K: Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 71:3196–3201. 2011. View Article : Google Scholar : PubMed/NCBI
43	Borovski T, Melo FD, Vermeulen L and Medema JP: Cancer stem cell niche: The place to be. Cancer Res. 71:634–639. 2011. View Article : Google Scholar : PubMed/NCBI
44	Al-Ostoot FH, Salah S, Khamees HA and Khanum SA: Tumor angiogenesis: Current challenges and therapeutic opportunities. Cancer Treat Res Commun. 28:1004222021. View Article : Google Scholar : PubMed/NCBI
45	Marmé D: The impact of anti-angiogenic agents on cancer therapy. J Cancer Res Clin Oncol. 129:607–620. 2003. View Article : Google Scholar : PubMed/NCBI
46	Elkhider A, Wang B, Ouyang X, Al-Azab M, Walana W, Sun X, Li H, Tang Y, Wei J and Li X: Aquaporin 5 promotes tumor migration and angiogenesis in non-small cell lung cancer cell line H1299. Oncol Lett. 19:1665–1672. 2020.PubMed/NCBI
47	Hou SY, Li YP, Wang JH, Yang SL, Wang Y, Wang Y and Kuang Y: Aquaporin-3 inhibition reduces the growth of NSCLC cells induced by hypoxia. Cell Physiol Biochem. 38:129–140. 2016. View Article : Google Scholar : PubMed/NCBI
48	Marlar S, Jensen HH, Login FH and Nejsum LN: Aquaporin-3 in cancer. Int J Mol Sci. 18:21062017. View Article : Google Scholar : PubMed/NCBI
49	Graziano AC, Avola R, Pannuzzo G and Cardile V: Aquaporin1 and 3 modification as a result of chondrogenic differentiation of human mesenchymal stem cell. J Cell Physiol. 233:2279–2291. 2018. View Article : Google Scholar
50	Zhou Y, Wang Y, Wen J, Zhao H, Dong X, Zhang Z, Wang S and Shen L: Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway. Oncotarget. 7:16529–16541. 2016. View Article : Google Scholar : PubMed/NCBI
51	Wang Y, Wu G, Fu X, Xu S, Wang T, Zhang Q and Yang Y: Aquaporin 3 maintains the stemness of CD133+ hepatocellular carcinoma cells by activating STAT3. Cell Death Dis. 10:4652019. View Article : Google Scholar : PubMed/NCBI
52	Xu H, Xu Y, Zhang W, Shen L, Yang L and Xu Z: Aquaporin-3 positively regulates matrix metalloproteinases via PI3K/AKT signal pathway in human gastric carcinoma SGC7901 cells. J Exp Clin Cancer Res. 30:862011. View Article : Google Scholar : PubMed/NCBI
53	Chen J, Wang T, Zhou YC, Gao F, Zhang ZH, Xu H, Wang SL and Shen LZ: Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer. J Exp Clin Cancer Res. 33:382014. View Article : Google Scholar : PubMed/NCBI