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Plant Science Today (PST)

Research Articles

Early Access

Zingiber zerumbet rhizome extract inhibits cell migration and induces apoptosis in MCF-7 breast cancer cells

DOI
https://doi.org/10.14719/pst.12839
Submitted
20 November 2025
Published
14-04-2026

Abstract

Zingiber zerumbet (L.) Roscoe ex Sm. (Zingiberaceae) is used in an extensive range of conventional medicine practices. This study demonstrates the chemical constituents of the rhizome extract of Z. zerumbet and evaluates its antiradical, antiproliferative and apoptosis-inducing potential against breast cancer cells. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified zerumbone (94.88 ± 0.02) to be the main component of the methanol extract along with humulene epoxide (3.05 ± 0.06) and caryophyllene oxide (2.07 ± 0.04). The extract exhibited notable antiradical activity with IC50 value of 261.66 ± 0.20 and 159.45 ± 0.15µg/mL for DPPH and ABTS assays respectively. While the reducing power assay indicated effective activity in the range, 200–500µg/mL. Moreover, cell viability assay exhibited MCF-7 cells to be the most sensitive among the cell lines examined. DNA fragmentation analysis and Annexin V-Fluorescein Isothiocyanate/propidium iodide (Annexin V-FITC/PI) dual staining confirmed the induction of apoptosis in MCF-7 cells. The changes in nuclear morphology were further validated using 4′,6-diamidino-2-phenylindole (DAPI) staining. Additionally, the cell migration assay presented the anti-metastatic potential of the extract. Findings of this study demonstrated that Z. zerumbet exerts cytotoxic and apoptosis induction effects against MCF-7 cells, indicating its potential significance for future preclinical studies in breast cancer.

References

  1. 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29. https://doi.org/10.3322/caac.21254
  2. 2. Fridlender M, Kapulnik Y, Koltai H. Plant derived substances with anti-cancer activity: from folklore to practice. Front Plant Sci. 2015;6:163. https://doi.org/10.3389/fpls.2015.00799
  3. 3. Asma ST, Acaroz U, Imre K, Morar A, Shah SRA, Hussain SZ, et al. Natural products/bioactive compounds as a source of anticancer drugs. Cancers. 2022;14(24):6203. https://doi.org/10.3390/cancers14246203
  4. 4. Yob N, Jofrry SM, Affandi M, Teh L, Salleh M, Zakaria Z. Zingiber zerumbet (L.) Smith: a review of its ethnomedicinal, chemical and pharmacological uses. Evid Based Complement Alternat Med. 2011;2011:543216. https://doi.org/10.1155/2011/543216
  5. 5. Kalantari K, Moniri M, Boroumand Moghaddam A, Abdul Rahim R, Ariff A, Izadiyan Z, et al. A review of the biomedical applications of zerumbone and the techniques for its extraction from ginger rhizomes. Molecules. 2017;22(10):1645. https://doi.org/10.3390/molecules22101645
  6. 6. Nag A, Bandyopadhyay M, Mukherjee A. Antioxidant activities and cytotoxicity of Zingiber zerumbet (L.) Smith rhizome. J Pharmacogn Phytochem. 2013;2(3):102–8.
  7. 7. Koga AY, Beltrame FL, Pereira AV. Several aspects of Zingiber zerumbet: a review. Rev Bras Farmacogn. 2016;26:385–91. https://doi.org/10.1016/j.bjp.2016.01.006
  8. 8. Dellai A, Mansour HB, Limem I, Bouhlel I, Sghaier MB, Boubaker J, et al. Screening of antimutagenicity via antioxidant activity in different extracts from the flowers of Phlomis crinita Cav. ssp. mauritanica Munby from the center of Tunisia. Drug Chem Toxicol. 2009;32(3):283–92. https://doi.org/10.1080/01480540902882200
  9. 9. Habsah M, Amran M, Mackeen M, Lajis N, Kikuzaki H, Nakatani N, et al. Screening of Zingiberaceae extracts for antimicrobial and antioxidant activities. J Ethnopharmacol. 2000;72(3):403–10. https://doi.org/10.1016/S0378-8741(00)00223-3
  10. 10. Al-Amin M, Sultana GNN, Hossain CF. Antiulcer principle from Zingiber montanum. J Ethnopharmacol. 2012;141(1):57–60. https://doi.org/10.1016/j.jep.2012.01.046
  11. 11. Klaunig JE. Chemical carcinogenesis. In: Principles of Toxicology: Environmental and Industrial Applications. 2nd ed. Boca Raton: CRC Press; 2014. p. 259–85.
  12. 12. Trachootham D, Zhang W, Huang P. Oxidative stress and drug resistance in cancer. In: Drug Resistance in Cancer Cells. New York: Springer; 2009. p. 137–75. https://doi.org/10.1007/978-0-387-89445-4_7
  13. 13. Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013;12(12):931–47. https://doi.org/10.1038/nrd4002
  14. 14. Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim HW, Yoshihiro A, et al. Zerumbone markedly suppresses free radical generation, proinflammatory protein production and cancer cell proliferation accompanied by apoptosis. Carcinogenesis. 2002;23(5):795–802. https://doi.org/10.1093/carcin/23.5.795
  15. 15. Ali H, Hasi RY, Islam M, Haque MS, Alkhanani MF, Almalki AH, et al. Antioxidant, cytotoxic and apoptotic activities of the rhizome of Zingiber zerumbet Linn. in Ehrlich ascites carcinoma bearing Swiss albino mice. Sci Rep. 2022;12(1):12150. https://doi.org/10.1038/s41598-022-15498-8
  16. 16. Yang HL, Chen SJ, Pandey S, Wu IC, Chung YT, Vadivalagan C, et al. Skin hydration and anti-inflammatory potential of zerumbone from Zingiber zerumbet. J Funct Foods. 2023;111:105890. https://doi.org/10.1016/j.jff.2023.105890
  17. 17. Abd Rashid R, Pihie AL. The antiproliferative effects of Zingiber zerumbet extracts and fractions on human breast carcinoma cell lines. Malays J Pharm Sci. 2005;3(1):45–52.
  18. 18. Sehrawat A, Arlotti JA, Murakami A, Singh SV. Zerumbone causes Bax- and Bak-mediated apoptosis in human breast cancer cells. Breast Cancer Res Treat. 2012;136:429–41. https://doi.org/10.1007/s10549-012-2280-5
  19. 19. Kim S, Lee J, Jeon M, Lee JE, Nam SJ. Zerumbone suppresses the motility and tumorigenicity of triple negative breast cancer cells via inhibition of TGF-β1 signaling pathway. Oncotarget. 2015;7(2):1544–57. https://doi.org/10.18632/oncotarget.6441
  20. 20. Jeon M, Han J, Nam SJ, Lee JE, Kim S. Elevated IL-1β expression induces invasiveness of triple negative breast cancer cells and is suppressed by zerumbone. Chem Biol Interact. 2016;258:126–33. https://doi.org/10.1016/j.cbi.2016.08.021
  21. 21. Han J, Bae SY, Oh SJ, Lee J, Lee JH, Lee HC, et al. Zerumbone suppresses IL-1β-induced cell migration and invasion. Phytother Res. 2014;28(11):1654–60. https://doi.org/10.1002/ptr.5178
  22. 22. Sehrawat A, Sakao K, Singh SV. Notch2 activation is protective against anticancer effects of zerumbone in human breast cancer cells. Breast Cancer Res Treat. 2014;146:543–55. https://doi.org/10.1007/s10549-014-3059-7
  23. 23. Noviantari A, Efrilia M, Soleha M. Identification and anti-cancer testing results of subtropical ginger (Zingiber zerumbet) subcritical extraction. In: AIP Conf Proc. Melville: AIP Publishing; 2022. https://doi.org/10.1063/5.0107346
  24. 24. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–78. https://doi.org/10.1016/j.ejphar.2014.07.025
  25. 25. Adams RP, Sparkman OD. Review of identification of essential oil components by gas chromatography/mass spectrometry. J Am Soc Mass Spectrom. 2007;18(4):803–6. https://doi.org/10.1016/j.jasms.2007.01.001
  26. 26. Padalia RC, Verma RS, Chauhan A, Singh VR, Goswami P, Singh S, et al. Zingiber zerumbet (L.) Roscoe ex Sm. from northern India: potential source of zerumbone rich essential oil. Ind Crops Prod. 2018;112:749–54. https://doi.org/10.1016/j.indcrop.2018.01.006
  27. 27. Behera HT, Mojumdar A, Das SR, Jena S, Ray L. Production of N-acetyl chitooligosaccharide by novel Streptomyces chilikensis strain RC1830. Bioresour Technol Rep. 2020;11:100428. https://doi.org/10.1016/j.biteb.2020.100428
  28. 28. Jena S, Ray A, Banerjee A, Sahoo A, Nasim N, Sahoo S, et al. Chemical composition and antioxidant activity of essential oil from leaves and rhizomes of Curcuma angustifolia Roxb. Nat Prod Res. 2017;31(18):2188–91. https://doi.org/10.1080/14786419.2017.1278600
  29. 29. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26(9-10):1231–7. https://doi.org/10.1016/S0891-5849(98)00315-3
  30. 30. Berker KI, Güçlü K, Tor İ, Apak R. Comparative evaluation of Fe(III) reducing power-based antioxidant capacity assays. Talanta. 2007;72(3):1157–65. https://doi.org/10.1016/j.talanta.2007.01.019
  31. 31. Hanwar D, Dewi MS, Suhendi A, Trisharyanti DI, et al. Analysis of secondary metabolites profile of lempuyang gajah (Zingiber zerumbet Smith) ethanol extract using GC-MS. 2014.
  32. 32. Ravi A, Varghese S, Edayileveetil Krishnankutty R. Biocontrol activity of extract from Zingiber zerumbet for management of rhizome rot in Zingiber officinale caused by Pythium myriotylum. Arch Phytopathol Plant Prot. 2017;50(11-12):555–67. https://doi.org/10.1080/03235408.2017.1351181
  33. 33. Kumar S, Sharma VK, Yadav S, Dey S. Antiproliferative and apoptotic effects of black turtle bean extracts on human breast cancer cell line. Chem Cent J. 2017;11:1–10. https://doi.org/10.1186/s13065-017-0281-5
  34. 34. Ray A, Halder T, Jena S, Sahoo A, Ghosh B, Mohanty S, et al. Application of ANN model for prediction and optimization of coronarin D content in Hedychium coronarium. Ind Crops Prod. 2020;146:112186. https://doi.org/10.1016/j.indcrop.2020.112186
  35. 35. Prakash D, Suri S, Upadhyay G, Singh BN. Total phenol, antioxidant and free radical scavenging activities of some medicinal plants. Int J Food Sci Nutr. 2007;58(1):18–28. https://doi.org/10.1080/09637480601093269
  36. 36. Ud-Daula AS, Demirci F, Salim KA, Demirci B, Lim LB, Baser KHC, et al. Chemical composition and activities of essential oils from Etlingera fimbriobracteata (K. Schum.) R.M. Sm. Ind Crops Prod. 2016;84:189–98. https://doi.org/10.1016/j.indcrop.2015.12.034
  37. 37. Koleva II, Van Beek TA, Linssen JP, Groot A, Evstatieva LN. Screening of plant extracts for antioxidant activity. Phytochem Anal. 2002;13(1):8–17. https://doi.org/10.1002/pca.611
  38. 38. Hemn HO, Noordin MM, Rahman HS, Hazilawati H, Zuki A, Chartrand MS. Antihypercholesterolemic and antioxidant efficacies of zerumbone in cholesterol-fed rabbits. Drug Des Devel Ther. 2015;9:4173–208.
  39. 39. Wan Salleh WMNH, Kammil MF, Ahmad F, Sirat HM. Antioxidant and anti-inflammatory activities of essential oil and extracts of Piper miniatum. Nat Prod Commun. 2015;10(11):1934578X1501001151. https://doi.org/10.1177/1934578X1501001151
  40. 40. Delgado C, Mendez-Callejas G, Celis C. Caryophyllene oxide isolated from leaves of Hymenaea courbaril L. (Fabaceae) with antiproliferative effects on PC-3 prostate cancer cells. Molecules. 2021;26(20):6142. https://doi.org/10.3390/molecules26206142
  41. 41. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis. Nature. 1998;391(6662):43–50. https://doi.org/10.1038/34112
  42. 42. Aloqbi AA. A pathway to natural cancer therapy: exploring zerumbone's multitargeted anticancer actions. Int J Pharm Investig. 2025;15(3):225–32. https://doi.org/10.5530/ijpi.20250217
  43. 43. El Fagie RM, Yusoff NA, Lim V, Kamal NNSNM, Samad NA. Anti-cancer and anti-angiogenesis activities of zerumbone isolated from Zingiber zerumbet: a systematic review. Curr Res Nutr Food Sci. 2021;9(2):353–74. https://doi.org/10.12944/CRNFSJ.9.2.01
  44. 44. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on apoptotic lymphocytes triggers recognition by macrophages. J Immunol. 1992;148(7):2207–16. https://doi.org/10.4049/jimmunol.148.7.2207
  45. 45. Fan MJ, Wang IC, Hsiao YT, Lin HY, Tang NY, Hung TC, et al. Anthocyanins from black rice (Oryza sativa L.) demonstrate antimetastatic properties. Nutr Cancer. 2015;67(2):32738. https://doi.org/10.1080/01635581.2015.990576
  46. 46. Lee K, Seo I, Choi MH, Jeong D. Roles of mitogen-activated protein kinases in osteoclast biology. Int J Mol Sci. 2018;19(10):3004. https://doi.org/10.3390/ijms19103004
  47. 47. Xia Y, Lian S, Khoi PN, Yoon HJ, Joo YE, Chay KO, et al. Chrysin inhibits tumor promoter-induced MMP-9 expression in gastric cancer cells. PLoS One. 2015;10(4):e0124007. https://doi.org/10.1371/journal.pone.0124007
  48. 48. Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs) as a target for anticancer drugs. J Enzyme Inhib Med Chem. 2016;31(S1):177–83. https://doi.org/10.3109/14756366.2016.1161620

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