Heptyl prodigiosin from estuarine Zooshikella sp. RANM57 induces caspase-dependent apoptosis and suppresses clonogenic survival in androgen-independent prostate cancer cells
Year: 2026
Type: preprint
Abstract: Estuarine microbiomes are rich ecological niches for discovering novel secondary metabolites with therapeutic applications. This study focuses on the isolation, purification, structural elucidation, and antineoplastic evaluation of a red pigment from a marine microbial isolate. The bacterium Zooshikella sp. RANM57 was isolated from the Netravathi River estuary. Biomass was recovered using an alum-induced flocculation technique and solvent extraction, after which the primary pigment was purified via flash chromatography and structurally characterized using HRLCMS-QTOF and NMR spectroscopy. Anticancer potential was evaluated against human PC-3 prostate cancer cells using MTT and clonogenic assays. The underlying apoptotic mechanism was delineated using Annexin V/PI staining, Caspase-3 quantification, and TUNEL assays. The purified pigment was identified as the tripyrrole alkaloid heptyl prodigiosin based on HRLCMS-QTOF, UV-Vis/FT-IR profiling, and 1D NMR spectral concordance with reported prodiginine features. In vitro evaluations revealed significant dose-dependent cytotoxicity against PC-3 cells (IC 50 = 9.00 µg/mL), demonstrating high anticancer efficacy relative to cisplatin. Mechanistic profiling confirmed that cell death occurred exclusively via an intrinsic apoptotic cascade, as evidenced by significant phosphatidylserine externalization (17.60%), executioner Caspase-3 activation (52.45%), and terminal DNA fragmentation (21.25%), without inducing primary necrosis. Furthermore, treatment also reduced clonogenic survival after 24 h exposure and 8-day outgrowth. The successful isolation and characterization of heptyl prodigiosin from Zooshikella sp. RANM57 underscores the value of estuarine bacteria in natural product discovery. Our biological evaluations demonstrate that the compound functions as a precise, potent inducer of caspase-associated apoptosis, positioning this tripyrrole scaffold as a highly promising candidate for further anticancer pharmacological development.
Source: Research Square
Language: English
Subfield: Biotechnology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223788902