Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer

Abstract

The inhibitory action of prostaglandin D2 (PGD2) and its effect on the cell cycle were examined in cell lines SW480 and LS174T of human colon cancer. The growth of the cell lines were assessed 24 h and 48 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The growth of SW480 cells was inhibited 48 h, but not 24 h, after the addition of 1.0 microgram/ml, and 24 h and 48 h after the addition of 10.0 micrograms/ml, while that of LS174T was inhibited by both doses after 24 h and 48 h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24 h after the addition of 10.0 micrograms/ml PGD2. The cell cycle of LS174T cells was arrested at the G0 + G1 phase 24 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The correlation between hepatic metastasis and PGD2 concentration in human cancer tissue was examined. The mean value of PGD2 concentrations in the primary cancer tissue was significantly lower in the hepatic metastasis group than that in the group without hepatic metastasis. These findings suggest that measuring the PGD2 in cancer tissue may be useful for detecting and predicting the hepatic metastasis from human colorectal cancer.

Prostanoid receptor expression in colorectal cancer related to tumor stage, differentiation and progression

“…TXA 2 is involved in angiogenesis and subsequent development of tumor metastases, while PGI 2 displayed anti-cancerogenic effects in a murine cell model [4,25]. The DP receptor has been linked to inflammation which may represent a prestage to cancer, where DP1 shows anti-inflammatory effects and DP2 pro-inflammatory actions [26], although PGD 2 displayed anti-proliferative activity in-vitro [27]. Table V).…”

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention

“…3. PGD 2 treatment inhibited proliferation in colorectal tumor cell lines, an effect which was associated with cell-cycle arrest [97]. However, a later study demonstrated that both PGJ 2 and 15d-PGJ 2 (the metabolites of PGD 2 ) induced proliferation of colorectal cancer cells [98], suggesting a role for these prostanoid metabolites in tumor cell survival.…”

Carcinogenesis of malignant lesions of the gall bladder

“…The synthesis of prostanoids is mediated by COX-1 and COX-2, and the latter enzyme frequently is induced in response to inflammatory stimulators, lysolecithin, and cytokines in order to produce prostanoids [26,27,28]. Prostanoids and COX enzymes have also been shown to associate with carcinogenesis in various tumors, including gallbladder carcinoma [29,30,31,32,33,34]. Gallbladder carcinoma and colon carcinoma have several analogous characteristics: (1) important association with inflammatory diseases, cholecystitis, and inflammatory bowel diseases; (2) a high incidence of polypoid lesion; and (3) increased COX enzymes in lesion and a therapeutic action of NSAIDs.…”