Planta Med 2020; 86(06): 387-394
DOI: 10.1055/a-1129-7026
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Inhibitory Activity of Extract, Fractions, and Compounds from Zingiber montanum Rhizomes on the Migration of Breast Cancer Cells

Mohammad Al-Amin
1   Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
,
Nagla Mustafa Eltayeb
1   Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
2   Tropical Medicine Research Institute (TMRI), National Centre for Research (NCR), Khartoum, Sudan
,
Chowdhury Faiz Hossain
3   Department of Pharmacy, East West University, Aftabnagar, Dhaka, Bangladesh
,
Melati Khairuddean
4   School of Chemical Sciences, Universiti Sains Malaysia, Penang, Malaysia
,
Siti Sarah Fazalul Rahiman
5   Discipline of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
,
Salizawati Muhamad Salhimi
1   Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
› Institutsangaben
Gefördert durch: Universiti Sains Malaysia RUI grant: 1001/PFARMASI/8011003
Weitere Informationen

Publikationsverlauf

received 19. September 2019
revised 18. Februar 2020

accepted 26. Februar 2020

Publikationsdatum:
13. März 2020 (online)

Abstract

Zingiber montanum rhizomes are traditionally used for the treatment of numerous human ailments. The present study was carried out to investigate the inhibitory activity of the crude extract, chromatographic fractions, and purified compounds from Z. montanum rhizomes on the migration of MDA-MB-231 cells. The effect of the extract on cell migration was investigated by a scratch assay, which showed significant inhibition in a concentration-dependent manner. Vacuum liquid chromatography on silica gel afforded four fractions (Frs. 1 – 4), which were tested on cell migration in the scratch assay. Frs. 1 and 2 showed the most significant inhibition of MDA-MB-231 cell migration. The effect of the most potent fraction (Fr. 2) was further confirmed in a transwell migration assay. The study of Frs. 1 and 2 by gelatin zymography showed significant inhibition of MMP-9 enzyme activity. Chromatographic separation of Frs. 1 and 2 afforded buddledone A (1), zerumbone (2), (2E,9E)-6-methoxy-2,9-humuradien-8-one (3), zerumbone epoxide (4), stigmasterol (5), and daucosterol (6). In a cell viability assay, compounds 1 – 4 inhibited the viability of MDA-MB-231 cells in a concentration-dependent manner. The study of buddledone A (1) and zerumbone epoxide (4) on cell migration revealed that 4 significantly inhibited the migration of MDA-MB-231 cells in both scratch and transwell migration assays. The results of the present study may lead to further molecular studies behind the inhibitory activity of zerumbone epoxide (4) on cell migration and support the traditional use of Z. montanum rhizomes for the treatment of cancer.

Supporting Information

 
  • References

  • 1 Chun J, Kim YS. Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways. Chem Biol Interact 2013; 205: 212-221
  • 2 Lim TK. Zingiber montanum . In: Lim TK. ed. Edible medicinal and non-medicinal Plants, vol. 12. Cham: Springer; 2016: 443-468
  • 3 Kato E, Kubo M, Okamoto Y, Matsunaga Y, Kyo H, Suzuki N, Uebaba K, Fukuyama Y. Safety assessment of Bangle (Zingiber purpureum Rosc.) Rhizome extract: acute and chronic studies in rats and clinical studies in human. ACS Omega 2018; 3: 15879-15889
  • 4 Burkill IH. A Dictionary of the economic Products of the Malay Peninsula, Vols, 1 and 2. Kuala Lumpur: Ministry of Agriculture and Cooperative; 1966
  • 5 Vimala S, Norhanom AW, Yadav M. Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine. Br J Cancer 1999; 80: 110-116
  • 6 Al-Amin M, Sultana GNN, Hossain CF. Antiulcer principle from Zingiber montanum . J Ethnopharmacol 2012; 141: 57-60
  • 7 Sharma GJ, Thokchom DS. Antioxidant and radioprotective properties of Zingiber montanum (J. Konig) A. Dietr. Planta Med 2011; 77: 127
  • 8 Ozaki Y, Kawahara N, Harada M. Anti-inflammatory effect of Zingiber cassumunar Roxb. and its active principles. Chem Pharm Bull 1991; 39: 2353-2356
  • 9 Masuda T, Jitoe A, Mabry MJ. Isolation and structure determination of cassumunarins A, B and C: new anti-inflammatory antioxidants from a tropical ginger, Zingiber cassumunar . J Am Oil Chem Soc 1995; 72: 1053-1057
  • 10 Panthong A, Kanjanapothi D, Niwatananant W, Tuntiwachwuttikul P, Reutrakul V. Anti-inflammatory activity of compound D {(E)-4-(3′,4′-dimethoxyphenyl) but-3-en-2-ol} isolated from Zingiber cassumunar Roxb. Phytomedicine 1997; 4: 207-212
  • 11 Pithayanukul P, Tubprasert J, Wuthi-Udomlert M. In-vitro antimicrobial activity of Zingiber cassumunar (Plai) oil and a 5 % Plai oil gel. Phytother Res 2007; 21: 164-169
  • 12 Okonogi S, Chaiyana W. Enhancement of anticholinesterase activity of Zingiber cassumunar essential oil using a microemulsion technique. Drug Discov Ther 2012; 6: 249-255
  • 13 Iswantini D, Silitonga RF, Martatilofa E, Darusman LK. Zingiber cassumunar, Guazuma ulmifolia, and Murraya paniculata extracts as antiobesity: in vitro inhibitory effect on pancreatic lipase activity. Hayati J Biosci 2011; 18: 6-10
  • 14 Han AR, Lee EJ, Min HY, Kim HR, Lee SK, Seo EK. A potential cytotoxic principle of Zingiber cassumunar . Nat Prod Sci 2003; 9: 109-111
  • 15 Han AR, Min HY, Windono T, Jeohn GH, Jang DS, Lee SK, Seo EK. A new cytotoxic phenylbutenoid dimer from the rhizomes of Zingiber cassumunar . Planta Med 2004; 70: 1095-1097
  • 16 Matsuda H, Nakamura S, Iwami J, Li X, Pongpiriyadacha Y, Nakai M, Kubo M, Fukuyama Y, Yoshikawa M. Invasion inhibitors of human fibrosarcoma HT 1080 cells from the rhizomes of Zingiber cassumunar: structures of phenylbutanoids, cassumunols. Chem Pharm Bull 2011; 59: 365-370
  • 17 Lu JJ, Dang YY, Huang M, Xu WS, Chen XP, Wang YT. Anti-cancer properties of terpenoids isolated from Rhizoma curcumae – A review. J Ethnopharmacol 2012; 143: 406-411
  • 18 Khaw-On P, Banjerdpongchai R. Induction of intrinsic and extrinsic apoptosis pathways in the human leukemic MOLT-4 cell line by terpinen-4-ol. Asian Pac J Cancer Prev 2012; 13: 3073-3076
  • 19 Kalantari K, Moniri M, Moghaddam AB, Rahim RA, Ariff AB, Izadiyan Z, Mohamad R. A review of the biomedical applications of zerumbone and the techniques for its extraction from ginger rhizomes. Molecules 2017; 22: 1645
  • 20 Siddique H, Pendry B, Rahman MM. Terpenes from Zingiber montanum and their screening against multi-drug resistant and methicillin resistant staphylococcus aureus . Molecules 2019; 24: 385
  • 21 Liao YH, Houghton PJ, Hoult JRS. Novel and known constituents from Buddleja species and their activity against leukocyte eicosanoid generation. J Nat Prod 1999; 62: 1241-1245
  • 22 Matthes HWD, Luu B, Ourisson G. Cytotoxic components of Zingiber zerumbet, Curcuma zedoaria and C. domestica . Phytochemistry 1980; 19: 2643-2650
  • 23 Kitayama T, Okamoto T, Hill RK, Kawai Y, Takahashi S, Yonemori S, Yamamoto Y, Ohe K, Uemura S, Sawada S. Chemistry of zerumbone. 1. simplified isolation, conjugate addition reactions, and a unique ring contracting transannular reaction of its dibromide. J Org Chem 1999; 64: 2667-2672
  • 24 Jang DS, Seo EK. Potentially bioactive two new natural sesquiterpenoids from the rhizomes of Zingiber zerumbet . Arch Pharm Res 2005; 28: 294-296
  • 25 Sadhu SK, Khatun A, Ohtsuki T, Ishibashi M. First isolation of sesquiterpenes and flavonoids from Zingiber spectabile and identification of zerumbone as the major cell growth inhibitory component. Nat Prod Res 2007; 21: 1242-1247
  • 26 Kojima H, Sato N, Hatano A, Ogura H. Sterol glucosides from Prunella vulgaris . Phytochemistry 1990; 29: 2351-2355
  • 27 Wang Q, Qiu P, Guan F, Shan Y, Yin M, Feng X, Liu F. A New isoflavane from Suaeda glauca . Chem Nat Compd 2018; 54: 38-40
  • 28 Govindan B, Johnson AJ, Viswanathan G, Ramaswamy V, Koshy KC, Baby S. Secondary metabolites from the unique bamboo, Melocanna baccifera . Nat Prod Res 2019; 33: 122-125
  • 29 Soares AD, Ferreira AG, Soares LR, Corsino J, Garcez FR, Garcez WS. Chemical study of leaves of Trichilia silvatica Meliaceae. Quím Nova 2014; 37: 1487-1490
  • 30 Han J, Bae SY, Oh SJ, Lee J, Lee JH, Lee H, Lee SK, Kil WH, Kim SW, Nam SJ, Kim S, Lee JK. Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells. Phytother Res 2014; 28: 1654-1660
  • 31 Chung IM, Kim MY, Park WH, Moon HI. Histone deacetylase inhibitors from the rhizomes of Zingiber zerumbet . Pharmazie 2008; 63: 774-776
  • 32 Ahmed Hamdi OA, Syed Abdul Rahman SN, Awang K, Abdul Wahab N, Looi CY, Thomas NF, Abd Malek SN. Cytotoxic constituents from the rhizomes of Curcuma zedoaria . ScientificWorldJournal 2014; 2014: 321943
  • 33 Yodkeeree S, Ampasavate C, Sung B, Aggarwal BB, Limtrakul P. Demethoxycurcumin suppresses migration and invasion of MDA-MB-231 human breast cancer cell line. Eur J Pharmacol 2010; 627: 8-15