Antitumor effects of geraniol on oral cancer

  • Jide Elsayad College of Science, Matrouh University, Mersa Matruh, Egypt
  • Najla Adeshina College of Science, Matrouh University, Mersa Matruh, Egypt
Keywords: geraniol, oral cancer, cell proliferation, cell migration, tumor growth


Background: Geraniol has been shown to possess therapeutic or preventive effects against various types of human cancers but not affect normal physiology through regulating cell cycle and apoptosis. However, the biological effects of geraniol on oral squamous cell carcinoma (OSCC) cells are unknown.

Methods: OSCC cell proliferation was measured by cell-counting kit-8 and colony formation assays. Cell migration was assessed by wound-healing assay. Apoptosis of OSCC cells was detected by TUNEL staining analysis. UM1 xenograft mouse model was used for determining the antitumor effects of geraniol in vivo.

Results: Geraniol treatment significantly suppressed OSCC cell proliferation and migration in vitro, and tumor growth in vivo in a time- and dose-dependent manner. Further investigation showed that geraniol treatment effectively induced OSCC apoptosis and blocked Phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling activation concurrently. We also found that geraniol administration at the dose of 100 and 250 mg/kg did not affect the body weight on tumor-bearing mice, demonstrating the safety of geraniol.

Conclusion: Geraniol may serve as a promising anticancer drug for the treatment of oral cancer.


Download data is not yet available.


Amarasinghe A, Usgodaarachchi US, Johnson NW, Warnakulasuriya S. High prevalence of lifestyle factors attributable for oral cancer, and of oral potentially malignant disorders in rural Sri Lanka. Asian Pac J Cancer Prev 2018; 19(9): 2485–92.

Jayant K, Deo MG. Oral cancer and cultural practices in relation to betel quid and tobacco chewing and smoking. Cancer Detect Prev 1986; 9(3–4): 207–13.

Kim SM. Human papilloma virus in oral cancer. J Korean Assoc Oral Maxillofac Surg 2016; 42(6): 327–36. doi: 10.5125/jkaoms.2016.42.6.327

Day TA, Davis BK, Gillespie MB, Joe JK, Kibbey M, Martin-Harris B, et al. Oral cancer treatment. Curr Treat Options Oncol 2003; 4(1): 27–41. doi: 10.1007/s11864-003-0029-4

Javed F, Al-Hezaimi K, Al-Rasheed A, Almas K, Romanos GE. Implant survival rate after oral cancer therapy: a review. Oral Oncol 2010; 46(12): 854–9. doi: 10.1016/j.oraloncology.2010.10.004

Chan KK, Glenny AM, Weldon JC, Furness S, Worthington HV, Wakeford H. Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy. Cochrane Database Syst Rev 2015; (12): CD010341. doi: 10.1002/14651858.CD010341.pub2

More Y, D’Cruz AK. Oral cancer: review of current management strategies. Natl Med J India 2013; 26(3): 152–8.

Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients 2020; 12(2): 457. doi: 10.3390/nu12020457

Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: a versatile source of anticancer drugs. Pharmacogn Rev 2011; 5(9): 1–12. doi: 10.4103/0973-7847.79093

Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 2013; 3(6): 439–59. doi: 10.1007/s13205-013-0117-5

Tiwari M, Kakkar P. Plant derived antioxidants – geraniol and camphene protect rat alveolar macrophages against t-BHP induced oxidative stress. Toxicol In Vitro 2009; 23(2): 295–301. doi: 10.1016/j.tiv.2008.12.014

Maczka W, Winska K, Grabarczyk M. One hundred faces of geraniol. Molecules 2020; 25(14): 3303. doi: 10.3390/molecules25143303

Rekha KR, Selvakumar GP, Sethupathy S, Santha K, Sivakamasundari RI. Geraniol ameliorates the motor behavior and neurotrophic factors inadequacy in MPTP-induced mice model of Parkinson’s disease. J Mol Neurosci 2013; 51(3): 851–62. doi: 10.1007/s12031-013-0074-9

Cho M, So I, Chun JN, Jeon JH. The antitumor effects of geraniol: modulation of cancer hallmark pathways (Review). Int J Oncol 2016; 48(5): 1772–82. doi: 10.3892/ijo.2016.3427

Burke YD, Stark MJ, Roach SL, Sen SE, Crowell PL. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 1997; 32(2): 151–6. doi: 10.1007/s11745-997-0019-y

Carnesecchi S, Schneider Y, Ceraline J, Duranton B, Gosse F, Seiler N, et al. Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells. J Pharmacol Exp Ther 2001; 298(1): 197–200.

Madankumar A, Jayakumar S, Gokuladhas K, Rajan B, Raghunandhakumar S, Asokkumar S, et al. Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis. Eur J Pharmacol 2013; 705(1–3): 148–55. doi: 10.1016/j.ejphar.2013.02.048

Chaudhary SC, Siddiqui MS, Athar M, Alam MS. Geraniol inhibits murine skin tumorigenesis by modulating COX-2 expression, Ras-ERK1/2 signaling pathway and apoptosis. J Appl Toxicol 2013; 33(8): 828–37. doi: 10.1002/jat.2739

Duncan RE, Lau D, El-Sohemy A, Archer MC. Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. Biochem Pharmacol 2004; 68(9): 1739–47. doi: 10.1016/j.bcp.2004.06.022

Wiseman DA, Werner SR, Crowell PL. Cell cycle arrest by the isoprenoids perillyl alcohol, geraniol, and farnesol is mediated by p21(Cip1) and p27(Kip1) in human pancreatic adenocarcinoma cells. J Pharmacol Exp Ther 2007; 320(3): 1163–70. doi: 10.1124/jpet.106.111666

Galle M, Crespo R, Kladniew BR, Villegas SM, Polo M, de Bravo MG. Suppression by geraniol of the growth of A549 human lung adenocarcinoma cells and inhibition of the mevalonate pathway in culture and in vivo: potential use in cancer chemotherapy. Nutr Cancer 2014; 66(5): 888–95. doi: 10.1080/01635581.2014.916320

Crespo R, Montero Villegas S, Abba MC, de Bravo MG, Polo MP. Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways. Biochem Cell Biol 2013; 91(3): 131–9. doi: 10.1139/bcb-2012-0076

Kim SH, Bae HC, Park EJ, Lee CR, Kim BJ, Lee S, et al. Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways. Biochem Biophys Res Commun 2011; 407(1): 129–34. doi: 10.1016/j.bbrc.2011.02.124

Yu SG, Hildebrandt LA, Elson CE. Geraniol, an inhibitor of mevalonate biosynthesis, suppresses the growth of hepatomas and melanomas transplanted to rats and mice. J Nutr 1995; 125(11): 2763–7.

He L, Mo H, Hadisusilo S, Qureshi AA, Elson CE. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J Nutr 1997; 127(5): 668–74. doi: 10.1093/jn/127.5.668

Vinothkumar V, Manoharan S, Sindhu G, Nirmal MR, Vetrichelvi V. Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 2012; 369(1–2): 17–25. doi: 10.1007/s11010-012-1364-1

Younis NS, Abduldaium MS, Mohamed ME. Protective effect of geraniol on oxidative, inflammatory and apoptotic alterations in isoproterenol-induced cardiotoxicity: role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR pathways. Antioxidants (Basel) 2020; 9(10): 977. doi: 10.3390/antiox9100977

Wu Y, Wang Z, Fu X, Lin Z, Yu K. Geraniol-mediated osteoarthritis improvement by down-regulating PI3K/Akt/NF-kappaB and MAPK signals: in vivo and in vitro studies. Int Immunopharmacol 2020; 86: 106713. doi: 10.1016/j.intimp.2020.106713

How to Cite
ElsayadJ., & AdeshinaN. (2023). Antitumor effects of geraniol on oral cancer. STEMedicine, 4(1), e155.
Research articles