Selective apoptotic cell death effects of oral cancer cells treated with destruxin B

Abstract

BackgroundRecent studies have revealed that destruxins (Dtx) have potent cytotoxic activities on individual cancer cells, however, data on oral cancer cells especial human are absent.MethodsDestruxin B (DB) was isolated and used to evaluate the selective cytotoxicity with human oral cancer cell lines, GNM (Neck metastasis of gingival carcinoma) and TSCCa (Tongue squamous cell carcinoma) cells, and normal gingival fibroblasts (GF) were also included as controls. Cells were tested with different concentrations of DB for 24, 48, and 72 h by MTT assay. Moreover, the mechanism of cytotoxicity was investigated using caspase-3 Immunofluorescence, annexin V/PI staining, and the expression of caspase-3, Bax, and Bcl-2 by western blotting after treated with different concentrations of DB for 72 h as parameters for apoptosis analyses.ResultsThe results show that DB exhibited significant (p < 0.01) and selective time- and dose-dependent inhibitory effects on GNM and TSCCa cells viability but not on GF cells. The data suggested that DB is capable to induce tumor specific growth inhibition in oral GNM and TSCCa cancer cells via Bax/Bcl-2-mediated intrinsic mitochondrial apoptotic pathway in time- and dose-dependent manners.ConclusionsThis is the first report on the anti-proliferation effect of DB in oral cancer cells. The results reported here may offer further evidences to the development of DB as a potential complementary chemotherapeutic target for oral cancer complications.

Destruxin B Suppresses Drug-Resistant Colon Tumorigenesis and Stemness Is Associated with the Upregulation of miR-214 and Downregulation of mTOR/β-Catenin Pathway

“…Our previous studies have demonstrated that DB treatment significantly suppressed tumorigenesis in different cancer types [ 13 , 14 , 15 , 27 , 28 ]. In this study, we examined the potential inhibitory effect of DB using 5-FU resistant colon cancer cells, induced by IGF1.…”

“…Thus, natural resources still remain as a valuable pool for anti-cancer drug discovery. Destruxin B (DB) is a cyclic depsipeptide produced by various species of fungi, and has been previously shown to inhibit proliferation and induce apoptosis in different cancer cells [ 12 , 13 , 14 ], making it a drug candidate for further development. Here, we showed that DB treatment not only suppressed colon tumorigenesis, but also CSC phenotypes.…”

“…For instance, Destruxin A, B, and E (DA, DB, and DE) represents a class of cyclic depsipeptides, with the ability to disrupt macromolecular syntheses (such as DNA, RNA, and protein), and inhibit and prevent viral infections [ 12 ]. Our team has previously discovered that Destruxin B exhibited anti-cancer activities both in vitro and in vivo by suppressing Wnt/β-catenin signaling [ 13 , 14 , 15 ]. We further our previous findings by investigating DB’s potential as an inhibitor of colon CSCs, since Wnt/β-catenin signaling plays an instrumental role in maintaining the stemness in intestinal stem cells, and its increased activity has been shown to contribute colon tumorigenesis [ 16 , 17 ].…”

Toward a Cancer Drug of Fungal Origin

“…The promising anticancer effects were revealed by the study of destruxin B in colorectal cancer models and specifically as an inhibitor of the Wnt/beta‐catenin/Tcf signaling pathway in colorectal cancer (Table ) and hepatocellular carcinoma cells with promising results. In addition, promising anticancer activity has also been recently demonstrated for destruxin B in oral cancer cells …”

Altered membrane rigidity via enhanced endogenous cholesterol synthesis drives cancer cell resistance to destruxins

“…Accordingly, destruxins are discussed as candidates for the development of novel therapeutics for the treatment of diverse maladies such as hepatitis B [ 21 – 24 ], liver fibrosis [ 25 ], osteoporosis [ 26 ] or Alzheimer’s disease [ 27 ]. In the field of cancer research, destruxins have been investigated in vitro for their therapeutic potential against oral carcinomas [ 28 ], leukemia [ 29 – 31 ], lymphomas [ 32 ], non-small cell lung cancer [ 33 ], hepatocellular carcinoma especially in combination with the tyrosine kinase inhibitor sorafenib [ 34 ], and colorectal cancer [ 20 ]. Additionally, significant anticancer activity of dtxB was reported in vivo against colorectal cancer in two studies using HT-29 xenograft mouse models without observing any dtxB-related adverse effects [ 35 , 36 ].…”