Breast Cancer Migration and Proliferation Inhibitory and Antibiotic Secondary Metabolites from The Egyptian Olive Tree Endophytic Fungus Penicillium citrinum

Abstract

Objectives:The main aim of this study is to discover fungal endophytes associated with the Egyptian native olive tree Olea europaea as new sources for breast cancer control and investigate the chemistry and bioactivity of the fermentation metabolites of the identified active fungal species. Methods: Screening of multiple cultured Egyptian olive treeassociated fungal endophyte extracts identified Penicillium citrinum extract in breast cancer proliferation assays. Bioassay-guided isolation of the fungus P. citrinum extract identified four known metabolites 1-4. Their structure identity was established by different 1D and 2D NMR analyses. Compounds were tested for antiproliferative activity against the human breast cancer cell lines BT-474, MDA-MB-231 and MDA-MB-468using MTT assay and antimigratory activity against the human breast cancer cell lines MDA-MB-231 using wound healing assay. The antimicrobial activity of 1-3 was assessed using modified Kirby-Bauer disc diffusion method against multiple Gram positive and negative bacteria and fungi. Results: NMR analyses identified 1 as the known mycotoxin citrinin and the three different pyrrolidine alkaloids: 2-(hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine (2), scalusamide A (3) and perinadine A (4). Compounds 2-4 showed significant antiproliferative activity against the human triple negative breast cancer cell line MDA-MB-231 with IC 50 values of 10.6, 14.8 and 17.7 µM, respectively. Prerinadine (3) significantly suppressed the HGF-induced cell migration in a dose dependent manner with IC 50 9.7. Citrinin (1) exerted remarkable antibiotic activity against Gram (+) and Gram (-) bacteria and was even up to several-fold those of tetracycline standard. Conclusion: Egyptian olive tree endophytes are valuable sources for biologically active natural products.

Endophytic Fungi of Olive Tree

“…A strain of Penicillium chrysogenum was found to produce the bioactive indole alkaloids meleagrin, roquefortine C, and dehydrohistidyltryptophenyl-diketopiperazine [ 42 ]. Moreover, from the same location of the Egyptian oasis of Siwa, an isolate of Penicillium citrinum was reported to produce the polyketide mycotoxin citrinin, along with the pyrrolidine alkaloids 2-(hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4 H -pyrrolo[2,1- b ]-1,3-oxazine, scalusamide A, and perinadine A [ 36 ].…”

In Vitro Tumor Cell Growth Inhibition Induced by Lophocereus marginatus (DC.) S. Arias and Terrazas Endophytic Fungi Extracts

“…The isolated strains of P. citrinum , PME-H001 and PME-H002, showed comparable cytotoxic activity, probably due to the production of similar compounds, however the metabolite profiles must be analyzed for confirmation. On the other hand, the anticancer activity of this species has been reported against different tumor cell lines, including A549, Hela, HepG2, L5178Y, MOLT-4, MCF-7, BT-474, and MDA-MB-231 and different compounds have been identified as being responsible for this activity, such as penicillocitrin A, 2-(2-acetyl-hydrazinyl) benzoic acid, 2-pyruvoylaminobenzamide, secalonic acid A, citriquinochroman, pyrrolidine alkaloids, pencitrin, and penicitrinone E [ 37 , 38 , 39 , 40 , 41 ]. In our study, Cladosporium sp.…”

In Vitro Antitumor Activity of Endophytic Fungi Isolated From the Mexican Cactus Pachycereus Marginatus (DC.) Britton & Ros

“…The isolated strains of P. citrinum PME-H001 and PME-H002, showed differential cytotoxic activity, which is consistent with other studies evidencing that the medicinal properties of endophytic fungi vary, despite they belong to the same genus and are isolated from the same host [37]. On the other hand, the anticancer activity of this species has been reported against different tumor cell lines such as A549, Hela, HepG2, L5178Y, MOLT-4, MCF-7, BT-474, and MDA-MB-231, identifying different compounds responsible for the activity, such as penicillocitrin A, citriquinochroman, citrinin, scalusamide A, perinadine A, pencitrin, and pencitrinol [37][38][39][40][41].…”