Maia, A. I. V. | bioRxiv Science

bioRxiv2025

Anticancer potential of piericidin A1 and derivatives isolated from Streptomyces sp. associated with Palythoa variabilis from Brazilian Reefs

Marine holobionts are prolific sources of bioactive natural products. Previously, our group investigated cytotoxic compounds in zoantharians of the genus Palythoa and, herein, we further explored the anticancer potential of marine bacteria associated with P. variabilis. After isolating 10 culturable bacterial strains, we screened for cytotoxic activity on metastatic prostate tumor cells (PC-3/M) using the MTT assay. The crude extract of one of the strains (BRA-035), identified as Streptomyces sp., was selected due to its bioactivity profile and submitted to cytotoxicity-guided fractionation. This approach allowed us to isolate piericidin A1 and identify other 2 piericidin derivatives. Piericidin A1 displayed a wide range of potency, with IC50 varying from pM to low nM for several tumor cells (OVCAR, PC-3, PC-3/M, HCT-116) or non active (IC50 >12uM) for leukemia cell line (HL-60) and murine melanoma (B16-F10). Overall, our findings demonstrate that P. variabilis hosts bacteria with biotechnological potential, confirming piericidin A1 as a promising candidate for anticancer applications.

pharmacology and toxicology↗

bioRxiv2025

Establishment and functional characterization of bovine endometrial epithelial organoids

Pre-implantation embryonic loss constitutes a major barrier to reproductive efficiency in livestock, yet the extrinsic determinants of embryonic survival remain poorly defined. Intra-organoid fluid (IOF) faithfully recapitulates native tissue secretions across multiple organ systems. We hypothesized that bovine endometrial epithelial organoids (BEEO) would produce IOF that mirrored in vivo uterine luminal fluid composition and extend embryo culture duration in vitro. We pursued three objectives: (a) establish and morphologically characterize BEEO, (b) define BEEO transcriptomic and secretory responses to estradiol (E2), medroxyprogesterone acetate (MPA), and interferon-tau (IFN{tau}), and (c) determine whether BEEO-derived IOF can support in vitro embryonic development beyond Day 8 (hatched blastocyst stage) under conventional culture conditions. BEEO were established from primary endometrial tissue (n=4) and maintained a stable epithelial phenotype through multiple passages. Transcriptomic profiling revealed robust responses to stimulation, with E2, MPA, and IFN{tau} inducing distinct gene expression programs consistent with in vivo effects. IOF metabolomic analysis confirmed hormone-dependent regulation of IOF secretory output, with E2+MPA (diestrus mimic) enhancing the production of metabolites implicated in conceptus development. Remarkably, IOF from diestrus mimic-stimulated BEEO, despite being diluted approximately seven-fold in PBS, maintained embryo survival rates comparable to optimized commercial medium, and exceeded PBS-only controls. These findings position BEEO as a physiologically relevant model for dissecting maternal-embryo interactions in vitro and identifying targets to improve fertility in cattle and other livestock.

cell biology↗