Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo

Abstract

The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer. ' 2009 UICC

MK615, A Compound Extract from the Japanese Apricot “Prunus mume” Inhibits In vitro Cell Growth and Interleukin-8 Expression in Non-small Cell Lung Cancer Cells

“…Together with previous studies demonstrating the MK615 anti-tumor activities in various cancer types [4][5][6][7][8][9][10], our results strengthen the evidence indicating that MK615 is an anti-tumor agent. Further in vivo studies will be necessary to evaluate the therapeutic efficacy of MK615 in NSCLC.…”

“…MK615 contains several triterpenoids including triterpene acids (e.g., oleanolic acid and ursolic acid) and phytosterols (e.g., ß-sitosterol) [9,18,19], which are widely present in natural foods and plants [20]. Given that these triterpenoids have been shown to have anti-inflammatory [21,22] and anti-tumor activities [23][24][25][26], some triterpenoids in MK615 appear While MK615 inhibited the in vitro cell growth of the majority of the NSCLC cell lines tested, the growth-inhibitory effects varied among the cell lines, and some cell lines exhibited MK615 resistance.…”

“…Ume fruits contains many natural chemical substances including citric acid, malic acid and triterpenoids [3]. MK615 ( Figure 1B), a compound extract from Ume fruits, has been shown to have anti-tumor effects against various human cancers including malignant melanoma [4] and colon [5], breast [6], hepatocellular [7,8], esophageal [9] and pancreatic cancers [10]. However, the MK615 anti-tumor effects on lung cancer remain to be elucidated.…”

Chemopreventive Activity of Mediterranean Medicinal Plants

“…When either individually or as a mixturewere administered in rats, a significant reduction in the frequency of aberrant crypt foci in the group treated with the triterpenoid compounds plus DMH was recorded compared to those treated with DMH alone, suggesting that triterpenes have a protective effect against colon carcinogenesis (Furtado et al, 2008). In the study by Yamai et al (2009) the triterpenes enhanced conventional therapy in esophageal cancer and anti-tumor activity attribted to the powerful antioxidanteffects (Ovesná et al, 2006) and their ability to block angiogenesis (Sogno et al, 2009).…”

Simultaneous HPLC determination of pomolic, ursolic and euscaphic/tormentic acids in roots and rhizomes of variousPotentillaspecies

“…It interferes with tumorigenesis, metastasis, and angiogenesis and induces apoptosis and differentiation of tumor cells [14][15][16]. The chemo-preventive ability of ursolic acid has been confirmed in the studies on animal models in vivo [17][18][19][20][21]. Moreover, ursolic acid inhibits experimental metastasis of esophageal carcinoma [16,20].…”