Clostridium butyricum MIYAIRI 588 shows antitumor effects by enhancing the release of TRAIL from neutrophils through MMP-8

Abstract

Bacillus Calmette-Guérin (BCG) intravesical therapy against superficial bladder cancer is one of the most successful immunotherapies in cancer, though the precise mechanism has not been clarified. Recent studies have demonstrated urinary tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels to be higher in BCG-responsive patients than non-responders and shown that polymorphonuclear neutrophils (PMNs) migrating to the bladder after BCG instillation release large amounts of TRAIL. To establish a safer and more effective intravesical therapy than BCG, we examined whether other bacteria induced similar effects. We stimulated PMNs or peripheral blood mononuclear cells (PBMCs) with BCG or other bacteria, and then aliquots of the culture supernatants or cell lysates were assayed for TRAIL. We examined the signaling pathway regulating the release of TRAIL from PMNs and evaluated the antitumor effects of BCG or other bacteria in vitro and in vivo. We have found that Clostridium butyricum MIYAIRI 588 (CBM588) induces the release of endogenous TRAIL from PMNs as well as BCG. In addition, we have shown that matrix metalloproteinase 8 (MMP-8) is one of the key factors responsible for the release. Interestingly, TLR2/4 signaling pathway has been suggested to be important for the release of TRAIL by MMP-8. CBM588 has been proven to be as effective as BCG against cancer cells by inducing apoptosis in vivo as well as in vitro. Taken together, these results strongly suggest that CBM588 is promising for a safer and more effective therapy against bladder cancer.

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

“…178 There are many living biotherapeutic probiotics that have protective effects on colitis or cancer. Such as Clostridium butyricum MIYAIRI 588, 179,180 F. prausnitzii A2-165 181 and engineered Lactococcus lactis. 182 Targeting bile acids-microbiota axis using living biotherapeutic products for the prevention of CRC may be an effective strategy.…”

Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells

“…Based on our present results, TRAIL inducers may be candidates that can reduce the effective dose of NSAIDs. We previously reported that lactobacilli and Clostridium butyricum MIYAIRI 588 facilitated the production of TRAIL4748. These results suggest that the combination with NSAIDs and probiotics as a TRAIL inducer may be a useful strategy for cancer chemoprevention through the TRAIL-DR5 pathway.…”

Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, and metastatic colon tissue and colon biopsies from healthy donors

“…Экспрессия гена MMP-11 позитивно коррелирует как со стадиями КРР по классификации Дюкса, так и с метастазами в лимфоузлы, отдалёнными метастазами и экспрессией фактора роста эндотелия сосудов С [3]. Значение ММР-8 в развитии КРР ещё не изучено, однако недавние исследования продемонстрировали антиинвазивную роль ММР-8 при раке молочной железы и мочевого пузыря [9]. В настоящей работе мы сравнили уровни мРНК нескольких ММР (MMP-7, -8, -9, -11) в различных образцах КРР и нормальной ткани здоровых волонтеров.…”