Inhibitory Effects of Leaves of Guava (Psidium guajava) on TPA-Induced Inflammation and Tumor Promotion in Two-Stage Carcinogenesis in Mouse Skin


  • Ken Yasukawa Nihon University, 7-7-1, Narashinodai, Chiba 274-8555, Japan
  • Tomohito Kakegawa JosaiInternationalUniversity, 1Gumyo, Togane, Chba283-8555 ,Japan



 Guava, Psidium guajava, antitumor promotion, anti-inflammation, cancer prevention.


Cancer prevention offers the most cost-effective long-term health strategy. The methanol extract of the leaves of guava(Psidium guajava) exhibits marked antitumor activity in an in vivo two-stage carcinogenesis test in mice using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13- acetate (TPA) as a promoter. From the active fraction of the methanol extract, five triterpene acids, uvaol (1), ursolic acid (2), corosolic acid (3), asiatic aci (4), and oleanolic acid d (5), were isolated and identified. These compounds were evaluated for their inhibitory effects on TPA-induced inflammation (1 µg/ear) in mice, and showed marked anti-inflammatory effects, with a 50% inhibitory dose of 117–657 nmol/ear. The leaves of guava may therefore be effective for cancer prevention.


Yasukawa K. Edible and medicinal plants as cancer chemopreventive agents, In: ‘Drug discovery research in pharmacognosy’. Eds Vallisuta O, Olimat SM. InTech, Rijeka 2012; pp. 181‒208.

Yasukawa K. Edible and medicinal mushrooms as promising agents in cancer. In: ‘Drug discovery and development ― From molecules to medicine’, Eds Vallisuta O, Olimat SM. InTech, Rijeka 2015; pp. 39‒61.

Yasukawa K. Cancer chemopreventive agents: Natural pentacyclic triterpenoids. In: ‘Pentacyclic triterpenes as promising agents in cancer’. Ed Salvador JAR. Nova Science Publishers, New York 2010; pp. 127‒157.

Yasukawa K. Cancer chemopreventive agents: tetracyclic triterpenes promising as cancer, In: ‘Horizons in cancer research. Vol. 51’ Ed Watanabe HS, Nova Science Publisher, New York 2011; pp. 89‒113.

Gutiérrez RMP, Mitchell S, Solis RV. Psidium guajava: A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 2008; 117: 1‒27.

Sanda KA, grema HA, Geidam YA, Bukar-Kolo YM. Pharmacological aspects of Psidium guajava: an update. Int J Pharmacol 2011; 7: 316-324.

Mahato SB, Kundu AP. 13C NMR spectra of pentacyclic triterpenoids ―A compilation and some salient features. Phytochemistry 1994; 37: 1517-1575.

Li L-M, Pu J-X, Xiao W-L, Sun H-D. Triterpenes from Isodon xerophilus. Chinese J Nat Med 2012; 10: 307-310.

Cheng J-J, Zhang L-J, Cheng H-L, Chiou C-T, Lee I-J, Kuo Y-H. Cytotoxic hexacyclic triterpene acids from Euscaphis japonica. J Nat Prod 2010; 73: 1655-1658.

Yasukawa K, Takahashi H, Kitanaka S, Hirayama H, Shigemoto K. Inhibitory effect of an aqueous extract of Phellinus linteus on tumor promotion in mouse skin. Mushroom Sci Biotechnol 2007; 15: 97-101.

Akita A, Sun Y, Yasukawa K. Inhibitory effects of chaga (Inonotus obliquus) on tumor promotion in two-stage mouse skin carcinogenesis. J Pharm Nutr Sci 2015; 5: 71-76.

Yasukawa K, Sun Y, Kitanaka S, Tomizawa N, Miura M, Motohashi S. Inhibitory effect of the Rhizomes of Alpinia officinarum on TPA-induced inflammation and tumor promotion in two-stage carcinogenesis in mouse skin. J Nat Med 2008; 62: 374-378.

Yasukawa K, Yu SY, Tsutsumi S, Kurokawa M, Park YK. Inhibitory effects of Brazilian propolis on tumor promotion in two-stage mouse skin carcinogenesis. J Pharm Nutr Sci 2012; 2: 71-76.

Yasukawa K, Okuda S, Nobushi Y. Inhibitory effect of gymnema (Gymnema sylvestre) leaves on tumour promotion in two-stage mouse skin carcinogenesis. Evid-Based Complement Alternat Med 2014; 2014: 328684.

Yasukawa K, Kitanaka S, Kawata K, Goto K. Anti-tumor promoters phenolics and triterpenoid from Hippophae rhamnoides. Fitoterapia 2009; 80: 164-167.

Yasukawa K, Takido M, Takeuchi M, Nakagawa S. Effect of chemical constituents from plants on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Chem Pharm Bull (Tokyo) 1989; 37: 1071-1073.

Huang M-T, Ho C-T, Wang Z-Y, Ferraro T, Lou Y-R, Stauber K, Ma W, Georgiadis C, Laskin JD, Conney AH. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res 1994; 54: 701‒708.

Tokuda H, Ohigashi H,Koshimizu K,Ito Y. Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Letters 1986; 33: 279-285.

Ringborn T, Segura L, Noreen Y, Perera P, Bohlin L. Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis. J Nat Prod 1998; 61: 1212‒1215.

Subbaramaiah K, Michaluarth P, Sporn MB, Annenberg AJ. Ursolic acid inhibits cyclooxigenese-2 transcription in human mammary epithelial cells. Cancer Res 2000; 60: 2399‒2404.

You HJ, Choi CY, Kim JY, Park SJ, Hahm KS, Jeong HG. Ursolic acid enhances nitric oxide and tumor necrosis factor-α production via nuclear factor-κB activation in the resting macrophages. FEBS Lett 2001; 509: 156‒160.

Cha HJ, Park MT, Chung HY, Kim ND, Sato H, Seiki M, Kim K-W. Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT1080 human fibrosarcoma cells. Oncogene 1998; 16: 771‒778.

Yim E-K, Lee K-H, Namkoong S-E, Um S-J, Park J-S. Proteomic analysis of ursolic acid-induced apoptosis in cervical carcinoma cells. Cancer Lett 2006; 235: 209‒220.

Fujiki H, Sueoka E, Suganuma M. Tumor promoters: from chemicals to inflammatory proteins. J Cancer Res Clin Oncol 2013; 139: 1603‒1614.




How to Cite

Ken Yasukawa, & Tomohito Kakegawa. (2015). Inhibitory Effects of Leaves of Guava (Psidium guajava) on TPA-Induced Inflammation and Tumor Promotion in Two-Stage Carcinogenesis in Mouse Skin . Journal of Pharmacy and Nutrition Sciences, 5(4), 216–221.