Butyrate reduces liver metastasis of rat colon carcinoma cells in vivo and resistance to oxidative stress in vitro

Abstract

Injection of the rat colon carcinoma cell line CC531 into spleen of syngeneic rats results in considerable amounts of liver metastases within 14 days. We investigated whether preincubation of the cells with butyrate reduced their metastatic ability in vivo and whether this was accompanied by reduction in related properties such as secretion of metalloproteinases and their ability to withstand oxidative stress. Butyrate incubation reduced cell growth rate and initiated apoptosis in a dose- and time-related manner, but proliferation was retrieved when cultivation was continued in medium without butyrate. Splenic injection of butyrate treated, proliferating cells resulted in significantly reduced amounts of tumor mass compared to untreated cells. The butyrate treated cells were more susceptible to oxidative stress than control cells, as demonstrated by increased number of apoptotic cells and reduced cell growth after exposure to menadione. A reduction in cellular glutathione was found after prolonged incubation with butyrate. Butyrate appeared not to alter the secretion of active metalloproteinases from the cells although an apparent increase in proforms was demonstrated. Neither did butyrate alter the synthesis of metalloproteinase inhibitors. Lastly, a reduced adhesion of the tumor cells to collagen coated matrix was found after butyrate treatment. Thus, the inhibitory effects of butyrate on tumor malignancy are caused by a diversity of mechanisms.

Effects of a Bacterial Lipid Byproduct on Human Pulp Fibroblasts In Vitro

“…These findings indicated that GSH depletion might be one of the mechanisms underlying butyrate-induced cytotoxicity. Our results were in agreement with Li et al (27) who reported that treatment of butyrate in colon cancer cells reduces the cellular GSH levels. Recently, exposure of butyrate can deplete GSH in MCF-7 breast cancer cells (28).…”

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

“…The use of CC531 colon carcinoma cells in tumor metastasis models has been evaluated in several studies [19][20][21][22][23][24]. It has been shown that CC531 cells injected into the vena mesocolica are a reliable tumor metastasis model.…”

Acetylcholinesterase in intestinal cell differentiation involves G2/M cell cycle arrest

“…Although butyrate serves as a source of oxidative fuel for normal colonocytes, addition of it to neoplastic cells inhibits hyperproliferation and drives terminal differentiation and/or apoptosis [16 -18]. Consistent with its anticarcinogenic role in vitro, increased butyrate production is closely correlated with the reduction of tumor mass in animal models [35,36]. Although several studies have revealed that NaBT can induce apoptosis [37 -39], we suppose that NaBT-induced cell differentiation or apoptosis depends on its dosage.…”