Skip to content
2000
Volume 28, Issue 6
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their efficiency remains inadequate.

Objective

Rosmanol (RML) is a phenolic diterpene compound with antioxidant and anticancer activities. In the current research, the apoptotic efficacy of RML on methylnitronitrosoguanidine (MNNG)-induced GC model was determined.

Materials and Methods

The rats were allocated into four sets, ., normal control, MNNG (200 mg/kg bw) + NaCl, MNNG + RML (20 mg/kg), and RML (20 mg/kg) orally treated for 20 weeks.

Results

The results exposed that GC rats revealed higher (0.05) levels of TBARS and reduced antioxidant status in the stomach and liver tissues counter to other groups. In contrast, the TBARS level was substantially alleviated (0.05) and restored the antioxidant status in RML-administered rats. Histopathologic assessment of gastric tissue unveiled that an MNNG-induced group presented squamous cell carcinoma with keratin pearls. The administration of RML reduced GC incidence, and only mild dysplasia was observed. Further, RML alleviated Bcl-2, P13K, AKT, and HMGB1, as evidenced by RT-PCR and Western blot analysis.

Conclusion

Furthermore, RML triggered caspase-mediated mitochondrial apoptosis through the inactivation of the PI3K/AKT/HMGB1 pathway, eventually leading to GC cell death. This highlights that RML may be a potential natural antioxidant employed as a chemoprotective agent in GC rats.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073297703240613073134
2024-06-19
2025-09-11

  • From This Site

    /content/journals/cchts/10.2174/0113862073297703240613073134
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. GuoD. ZhangB. LiuS. JinM. Xanthohumol induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI3K/Akt/mTOR-kinase in human gastric cancer cells.Biomed. Pharmacother.20181061300130610.1016/j.biopha.2018.06.166 30119200
     [Google Scholar]
  2. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  3. CrewK.D. NeugutA.I. Epidemiology of gastric cancer.World J. Gastroenterol.200612335436210.3748/wjg.v12.i3.354 16489633
     [Google Scholar]
  4. RawlaP. BarsoukA. Epidemiology of gastric cancer: Global trends, risk factors and prevention.Gastroenterol. Rev.202320527128710.1038/s41575‑022‑00726‑3
     [Google Scholar]
  5. KimM.J. KimH. Anticancer effect of lycopene in gastric carcinogenesis.J. Cancer Prev.2015202929610.15430/JCP.2015.20.2.92 26151041
     [Google Scholar]
  6. BornscheinJ. MalfertheinerP. Gastric carcinogenesis.Langenbecks Arch. Surg.2011396672974210.1007/s00423‑011‑0810‑y 21611816
     [Google Scholar]
  7. PiazueloM.B. EppleinM. CorreaP. Gastric cancer: An infectious disease.Infect. Dis. Clin. North Am.2010244853869vii.10.1016/j.idc.2010.07.010 20937454
     [Google Scholar]
  8. Diaz-NietoR. Orti-RodríguezR. WinsletM. Post-surgical chemotherapy versus surgery alone for resectable gastric cancer.Cochrane Libr.20139CD00841510.1002/14651858.CD008415.pub2 23999923
     [Google Scholar]
  9. ObaK. PaolettiX. AlbertsS. BangY.J. BenedettiJ. BleibergH. CatalanoP. LordickF. MichielsS. MoritaS. OhashiY. PignonJ. RougierP. SasakoM. SakamotoJ. SargentD. ShitaraK. CutsemE.V. BuyseM. BurzykowskiT. Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: A meta-analysis.J. Natl. Cancer Inst.2013105211600160710.1093/jnci/djt270 24108812
     [Google Scholar]
  10. BastosJ. LunetN. PeleteiroB. LopesC. BarrosH. Dietary patterns and gastric cancer in a Portuguese urban population.Int. J. Cancer2010127243344110.1002/ijc.25013 19876925
     [Google Scholar]
  11. MaoQ.Q. XuX.Y. ShangA. GanR.Y. WuD.T. AtanasovA.G. LiH.B. Phytochemicals for the prevention and treatment of gastric cancer: Effects and mechanisms.Int. J. Mol. Sci.202021257010.3390/ijms21020570 31963129
     [Google Scholar]
  12. XuJ. LongY. NiL. YuanX. YuN. WuR. TaoJ. ZhangY. Anticancer effect of berberine based on experimental animal models of various cancers: A systematic review and meta-analysis.BMC Cancer201919158910.1186/s12885‑019‑5791‑1 31208348
     [Google Scholar]
  13. HassanalilouT. GhavamzadehS. KhaliliL. Curcumin and gastric cancer: A review on mechanisms of action.J. Gastrointest. Cancer201950218519210.1007/s12029‑018‑00186‑6 30725357
     [Google Scholar]
  14. DuttaS. MahalanobishS. SahaS. GhoshS. SilP.C. Natural products: An upcoming therapeutic approach to cancer.Food Chem. Toxicol.201912824025510.1016/j.fct.2019.04.012 30991130
     [Google Scholar]
  15. LucasL. RussellA. KeastR. Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal.Curr. Pharm. Des.201117875476810.2174/138161211795428911 21443487
     [Google Scholar]
  16. WeiG. HoC. A stable quinone identified in the reaction of carnosol, a major antioxidant in rosemary, with 2,2-diphenyl-1-picrylhydrazyl radical.Food Chem.200696347147610.1016/j.foodchem.2005.02.041
     [Google Scholar]
  17. CheungS. TaiJ. Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis.Oncol. Rep.20071761525153110.3892/or.17.6.1525 17487414
     [Google Scholar]
  18. AltinierG. SosaS. AquinoR.P. MencheriniT. LoggiaR.D. TubaroA. Characterization of topical antiinflammatory compounds in Rosmarinus officinalis L.J. Agric. Food Chem.20075551718172310.1021/jf062610+ 17288440
     [Google Scholar]
  19. del BañoM.J. LorenteJ. CastilloJ. Benavente-GarcíaO. del RíoJ.A. OrtuñoA. QuirinK.W. GerardD. Phenolic diterpenes, flavones, and rosmarinic acid distribution during the development of leaves, flowers, stems, and roots of Rosmarinus officinalis. Antioxidant activity.J. Agric. Food Chem.200351154247425310.1021/jf0300745 12848492
     [Google Scholar]
  20. DoolaegeE.H.A. RaesK. SmetK. AndjelkovicM. Van PouckeC. De SmetS. VerhéR. Characterization of two unknown compounds in methanol extracts of rosemary oil.J. Agric. Food Chem.200755187283728710.1021/jf071101k 17685542
     [Google Scholar]
  21. LaiC.S. LeeJ.H. HoC.T. LiuC.B. WangJ.M. WangY.J. PanM.H. Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways.J. Agric. Food Chem.20095722109901099810.1021/jf9025713 19856917
     [Google Scholar]
  22. ChengA.C. LeeM.F. TsaiM.L. LaiC.S. LeeJ.H. HoC.T. PanM.H. Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells.Food Chem. Toxicol.201149248549310.1016/j.fct.2010.11.030 21112365
     [Google Scholar]
  23. TabataK. KimM. MakinoM. SatohM. SatohY. SuzukiT. Phenolic diterpenes derived from Hyptis incana induce apoptosis and G(2)/M arrest of neuroblastoma cells.Anticancer Res.2012321147814789 23155243
     [Google Scholar]
  24. JiangD. XuJ. LiuS. NasserM. WeiW. MaoT. LiuX. ZouX. LiJ. LiX. Rosmanol induces breast cancer cells apoptosis by regulating PI3K/AKT and STAT3/JAK2 signaling pathways.Oncol. Lett.202122263110.3892/ol.2021.12892 34267823
     [Google Scholar]
  25. de OliveiraM.R. FerreiraG.C. SchuckP.F. Dal BoscoS.M. Role for the PI3K/Akt/Nrf2 signaling pathway in the protective effects of carnosic acid against methylglyoxal-induced neurotoxicity in SH-SY5Y neuroblastoma cells.Chem. Biol. Interact.201524239640610.1016/j.cbi.2015.11.003 26577515
     [Google Scholar]
  26. GuoY.J. LuoT. WuF. LiuH. LiH.R. MeiY.W. ZhangS.L. TaoJ.Y. DongJ.H. FangY. ZhaoL. Corilagin protects against HSV1 encephalitis through inhibiting the TLR2 signaling pathways in vivo and in vitro.Mol. Neurobiol.20155231547156010.1007/s12035‑014‑8947‑7 25367881
     [Google Scholar]
  27. OhgakiH. KawachiT. MatsukuraN. MorinoK. MiyamotoM. SugimuraT. Genetic control of susceptibility of rats to gastric carcinoma.Cancer Res.198343836633667 6861136
     [Google Scholar]
  28. JayakumarS. MadankumarA. AsokkumarS. RaghunandhakumarS. Gokula dhas, K.; Kamaraj, S.; Josephine Divya, M.G.; Devaki, T. Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats.Mol. Cell. Biochem.20123601-2516010.1007/s11010‑011‑1043‑7 21879312
     [Google Scholar]
  29. SongP. WuL. GuanW. Dietary nitrates, nitrites, and nitrosamines intake and the risk of gastric cancer: A meta-analysis.Nutrients20157129872989510.3390/nu7125505 26633477
     [Google Scholar]
  30. TsukamotoT. MizoshitaT. TatematsuM. Animal models of stomach carcinogenesis.Toxicol. Pathol.200735563664810.1080/01926230701420632 17654405
     [Google Scholar]
  31. NaginiS. Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention.World J. Gastrointest. Oncol.20124715616910.4251/wjgo.v4.i7.156 22844547
     [Google Scholar]
  32. KarimiN. RashediJ. Mahdavi PoorB. ArabiS. GhorbaniM. TahmasebpourN. AsgharzadehM. Cytotoxic effect of rosemary extract on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines.Gastroenterol. Hepatol. Bed Bench2017102102107 28702133
     [Google Scholar]
  33. ZhangL. JiaB. VeluP. WuH. Corilagin induces apoptosis and inhibits HMBG1/PI3K/AKT signaling pathways in a rat model of gastric carcinogenesis induced by methylnitronitrosoguanidine.Environ. Toxicol.20223751222123010.1002/tox.23478 35103375
     [Google Scholar]
  34. GanapathyE. PeramaiyanR. RajasekaranD. VenkataramanM. DhanapalS. Modulatory effect of naringenin on N-methyl-N'-nitro-N-nitrosoguanidine- and saturated sodium chloride-induced gastric carcinogenesis in male Wistar rats.Clin. Exp. Pharmacol. Physiol.200835101190119610.1111/j.1440‑1681.2008.04987.x 18565195
     [Google Scholar]
  35. FeiS.J. XiaoS.D. PengY.S. ChenX.Y. ShiY. Chemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in rats.Chin. J. Dig. Dis.20067313414010.1111/j.1443‑9573.2006.00258.x 16808793
     [Google Scholar]
  36. IkezakiS. NishikawaA. FurukawaF. KudoK. NakamuraH. TamuraK. MoriH. Chemopreventive effects of curcumin on glandular stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride in rats.Anticancer Res.200121534073411 11848501
     [Google Scholar]
  37. ManikandanP. MuruganR.S. PriyadarsiniR.V. VinothiniG. NaginiS. Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG.Life Sci.20108625-2693694110.1016/j.lfs.2010.04.010 20434464
     [Google Scholar]
  38. MuruganR.S. MohanK.V.P.C. UchidaK. HaraY. PrathibaD. NaginiS. Modulatory effects of black tea polyphenols on oxidant–antioxidant profile and expression of proliferation, apoptosis, and angiogenesis-associated proteins in the rat forestomach carcinogenesis model.J. Gastroenterol.200742535236110.1007/s00535‑007‑2018‑z 17530359
     [Google Scholar]
  39. VelmuruganB. NaginiS. Combination chemoprevention of experimental gastric carcinogenesis by s-allylcysteine and lycopene: Modulatory effects on glutathione redox cycle antioxidants.J. Med. Food20058449450110.1089/jmf.2005.8.494 16379561
     [Google Scholar]
  40. ZhaoY. LiuY. LanX.M. XuG.L. SunY.Z. LiF. LiuH.N. Effect of dendrobium officinale extraction on gastric carcinogenesis in rats.Evid. Based Complement. Alternat. Med.201620161810.1155/2016/1213090 28119756
     [Google Scholar]
  41. KannoS. TomizawaA. HiuraT. OsanaiY. ShoujiA. UjibeM. OhtakeT. KimuraK. IshikawaM. Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice.Biol. Pharm. Bull.200528352753010.1248/bpb.28.527 15744083
     [Google Scholar]
  42. SuzukiY.J. FormanH.J. SevanianA. Oxidants as stimulators of signal transduction.Free Radic. Biol. Med.1997221-226928510.1016/S0891‑5849(96)00275‑4 8958153
     [Google Scholar]
  43. DrakeI.M. DaviesM.J. MapstoneN.P. DixonM.F. SchorahC.J. WhiteK.L.M. ChalmersD.M. AxonA.T.R. Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals.Carcinogenesis199617355956210.1093/carcin/17.3.559 8631145
     [Google Scholar]
  44. HabermannK.J. GrünewaldL. van WijkS. FuldaS. Targeting redox homeostasis in rhabdomyosarcoma cells: GSH-depleting agents enhance auranofin-induced cell death.Cell Death Dis.2017810e306710.1038/cddis.2017.412 28981107
     [Google Scholar]
  45. LiuP. ChengH. RobertsT.M. ZhaoJ.J. Targeting the phosphoinositide 3-kinase pathway in cancer.Nat. Rev. Drug Discov.20098862764410.1038/nrd2926 19644473
     [Google Scholar]
  46. LiX. ZhuF. JiangJ. SunC. WangX. ShenM. TianR. ShiC. XuM. PengF. GuoX. WangM. QinR. Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells.Cancer Lett.2015357121923010.1016/j.canlet.2014.11.026 25444914
     [Google Scholar]
/content/journals/cchts/10.2174/0113862073297703240613073134
Loading
Rosmanol Triggers Apoptosis Against MNNG-induced Gastric Carcinogenesis in Rats through Attenuation of the P13K/AKT/HMBG1 Signaling Pathway
Comb Chem High Throughput Screen 28, 988 (2025); https://doi.org/10.2174/0113862073297703240613073134
/content/journals/cchts/10.2174/0113862073297703240613073134
/content/journals/cchts/10.2174/0113862073297703240613073134
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): antioxidants; apoptosis; gastric cancer; methylnitronitrosoguanidine; Rosmanol

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test