Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Abstract

The antitumor effect of indomethacin on Colon 26, Meth-A and FM3A tumors was investigated in mice. The prostaglandin E 2 content in tumor tissues was assayed to find out if indomethacin acts on tumors, and the telomerase activity in tumors and somatic tissues (testis, liver, spleen and colon) was also monitored during indomethacin treatment. Growth of Colon 26, Meth-A and FM3A tumors was significantly (P< < < <0.001-0.05) suppressed by indomethacin compared to the untreated controls. The prostaglandin E 2 content in the three tumors was markedly (P< < < <0.001) reduced by indomethacin. Telomerase activity in Colon 26 and FM3A tumors was significantly (P< < < <0.001) lower than that of untreated tumors (80% and 45% decrease versus the controls, respectively), and the activity in Meth-A tumor was slightly decreased (10% decrease versus the control) by indomethacin. Telomerase activity in the somatic tissues was not significantly affected by indomethacin. In summary, this study shows the effectiveness of indomethacin as an antitumor agent against three types of tumors, and suggests that indomethacin affects telomerase activity in tumors in vivo.Key words: Indomethacin -Prostaglandin E 2 -Telomerase activity -Fluorescence-based telomeric repeat amplification protocolThe antitumor effect of indomethacin on tumors in cancer patients 1, 2) and in animals 3, 4) has been described. We previously showed that indomethacin suppresses the growth of Colon 26 tumor in mice by enhancing the cellular immune function and improving cancer cachexia. 5)Indomethacin does not have a cytotoxic effect on Colon 26 tumor cells in vitro, 5) but it may have an antitumor effect via immunological pathways. We previously reported that indomethacin treatment of tumors reduces tumor size less in nude mice (deficient in T-lymphocytes) than in normal mice, compared with untreated tumors. 6)Although these results indicate that the effectiveness of indomethacin as an antitumor agent is, at least in part, due to its modification of T-cell-mediated immune functions, the precise mechanism of tumor growth suppression by indomethacin remains unknown.Recent studies have shown that many proliferating tumor cells retain a certain level of telomerase activity. [7][8][9] We previously reported that tumor growth in Colon 26-bearing mice is significantly suppressed by indomethacin treatment compared with the untreated controls, and that the telomerase activity declines preferentially in tumor tissues, while telomerase activity in somatic tissues is not significantly affected by indomethacin treatment.10) More recently, Kido et al. 11) reported that tumor size reduction by cisplatin treatment correlates with a decline in telomerase activity in tumor tissues.In this study, we transplanted Colon 26, Meth-A and FM3A tumors into normal mice to assess if the effect of indomethacin is independent of tumor cell type. Prostaglandin E 2 synthesis is inhibited by indomethacin, and therefore we measured the prostaglandin E 2 content in tumors to confirm the effect of ind...

Raman spectra of high‐density, low‐density, and linear low‐density polyethylene pellets and prediction of their physical properties by multivariate data analysis

“…Prostaglandins have important physiologic functions such as mediating bone homeostasis and maintaining gastric epithelium, but are also potent sensitizers of primary afferent fibers such as when released during inflammation 75, 76. Tumors such as the colon 26 and 2472 sarcoma cell lines used in the present study release PGs77 or express COX‐2, however other tumors such as malignant melanomas in general do not express COX‐2 nor produce PG 78. Therefore, the phenotype of a given tumor cell line, the type of proteins, cytokines and factors that tumor cells secrete as well as its ability to remodel bone, probably plays a role in determining the type and severity of pain produced by different tumor types.…”

Nonsteroidal Anti-inflammatory—Organometallic Anticancer Compounds

“…The two NSAIDS considered for this study, indomethacin ( 1 , 2-{1-[(4-chlorophenyl)­carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}­acetic acid) and diclofenac ( 2 , 2-(2,6-dichloranilino)­phenylacetic acid) (Figure ), are efficient inflammation modulators used to treat painful conditions and are also shown to exhibit promising anticancer properties. ,,,− They are both classified as phenylalkanoic acids presenting an easy derivatizable carboxylic group. Previous reports indicate that modification of the carboxylic group does not impair biological activity. − Monodentate pyridine- and phosphine-based ligands modified with indomethacin and diclofenac were prepared as shown in Scheme .…”