Nurulita, N. A. | bioRxiv Science

bioRxiv2025

Anticancer potential of soil-associated actinobacterium DHE 6-7 isolated from Enggano Island, Indonesia

The growing demand for pharmaceuticals has driven a shift towards developing medicinal products through bioprospecting by utilising sustainable sources. This involves exploring the potential of beneficial bacteria, such as Actinobacteria, known for producing diverse secondary metabolites with medicinal applications. In a previous study, 422 Actinobacteria were successfully isolated from Lombok, Bali, and Enggano Islands in Indonesia, and subjected to various bioactivity tests. Notably, Isolate DHE 6-7 from Enggano Island showed promising potential as a drug candidate. This study aimed to evaluate anticancer activity of DHE 6-7 isolates in T47D breast cancer cell lines and pinpoint the key metabolite contributing to its anticancer activity. The secondary metabolites from the DHE 6-7 culture were extracted using ethyl acetate by liquid-liquid extraction and its bioactive compound was analysed using thin layer chromatography. Subsequently, the extract underwent cytotoxic and antiproliferative assays in T47D cells. While Actinomycin-D was previously identified as a major bioactive compound in methanolic extract of DHE 6-7 isolate, this study confirmed that ethyl acetate extraction was able to retain the Actinomycin-D content from DHE 6-7 isolate. Interestingly however, the ethyl acetate extract of DHE 6-7 (EAE of DHE 6-7) showed superior cytotoxic activity in T47D cells compared to actinomycin-D alone. This may suggest the contribution of additional secondary metabolites in the EAE of DHE 6-7 to its anticancer activity. Notably, the combination of the EAE of DHE 6-7 isolate and 5-FU (5-fluorouracil) exhibited a synergistic effect, indicating the potential use of these compound(s) as a co-chemotherapeutic agent.

microbiology↗

bioRxiv2024

Zbtb38 inhibits apoptosis by transcriptionally regulating XIAP expression

The X-linked inhibitor of apoptosis protein (XIAP) is a key suppressor of apoptosis, crucial for cellular differentiation, embryogenesis, and cancer progression. However, its upstream regulatory mechanisms remain poorly understood. Here, we demonstrate that the zinc finger transcription factor Zbtb38, a negative regulator of apoptosis, modulates XIAP expression in both loss- and gain-of-function experiments, irrespective of p53 expression. Notably, XIAP overexpression rescues the apoptosis induced by Zbtb38 knockdown, indicating that Zbtb38-associated apoptosis is at least partially XIAP-dependent. Mechanistically, Zbtb38 binds to E-box motifs within upstream regulatory regions of XIAP and activates its transcription. During embryonic stem (ES) cell differentiation and embryogenesis, Zbtb38 depletion increases apoptosis and reduces XIAP and Bcl-2 expression, underscoring their functional relevance in these processes. Analysis of human tumor datasets reveals a strong positive correlation between ZBTB38 and XIAP expression, with elevated ZBTB38 levels associated with high-grade malignancies. Furthermore, Zbtb38 knockdown induces apoptosis in cancer cells with reduced XIAP expression, regardless of p53 expression. Collectively, these findings uncover a novel Zbtb38-XIAP axis that regulates apoptosis during cellular differentiation, development, and oncogenesis, and highlight its therapeutic potential in XIAP-driven and p53-deficient tumors.

cell biology↗