RESUMEN
Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas.
Asunto(s)
Apoptosis , Linfocitos B , Herpesvirus Humano 4 , Activación Viral , Humanos , Herpesvirus Humano 4/efectos de los fármacos , Herpesvirus Humano 4/fisiología , Activación Viral/efectos de los fármacos , Linfocitos B/efectos de los fármacos , Linfocitos B/virología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Replicación Viral/efectos de los fármacos , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Antivirales/farmacología , Ascomicetos/efectos de los fármacos , Linfoma de Células B/virología , Linfoma de Células B/tratamiento farmacológico , Latencia del Virus/efectos de los fármacosRESUMEN
Two new berkeley meroterpenoids (1 and 2), along with seven known compounds (3â9) were isolated from a fungus, Penicillium sp. SSW03M2 GY derived from a sediment at Seosan bay, South Korea. Chemical structures of the isolated compounds were elucidated on the basis of 1D, 2D NMR, HRESIMS, and optical rotation. All the isolated compounds, 1 showed anti-virulence activity by significantly inhibiting α-toxin (Hla) secreted by methicillin-resistant Staphylococcus aureus without its growth inhibition.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Penicillium , Penicillium/química , Estructura Molecular , Espectroscopía de Resonancia Magnética , República de CoreaRESUMEN
A new oxazole-type compound (1), named macrooxazole E, and three known macrooxazoles A-C (2-4), were isolated from ethyl acetate (EtOAc) extracts of Phoma sp. JS0228 cultures, an endophytic fungus of Morus alba (M. alba). Structures of the isolated compounds were determined using spectroscopic methods, such as 1 D- and 2 D-nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Macrooxazole E (1) differed from macrooxazole C only in the presence of methyl carboxylate instead of free carboxylic acid. Macrooxazole C showed moderate anti-proliferative activities against human breast cancer (MCF-7) and prostate cancer (LNCaP) cell lines with IC50 values of 0.29 mM and 0.36 mM, respectively. This study presents the possibility of the endophytic fungus Phoma sp. JS0228 to produce new bioactive natural compounds.