Endophytic fungi are microorganisms that exist almost ubiquitously inside the various tissues of living plants where they act as an important reservoir of diverse bioactive compounds. Recently, endophytic fungi have drawn tremendous attention from researchers; their isolation, culture, purification, and characterization have revealed the presence of around 200 important and diverse compounds including anticancer agents, antibiotics, antifungals, antivirals, immunosuppressants, and antimycotics. Many of these anticancer compounds, such as paclitaxel, camptothecin, vinblastine, vincristine, podophyllotoxin, and their derivatives, are currently being used clinically for the treatment of various cancers (e.g., ovarian, breast, prostate, lung cancers, and leukemias). By increasing the yield of specific compounds with genetic engineering and other biotechnologies, endophytic fungi could be a promising, prolific source of anticancer drugs. In the future, compounds derived from endophytic fungi could increase treatment availability and cost effectiveness. This comprehensive review includes the putative anticancer compounds from plant-derived endophytic fungi discovered from 1990 to 2020 with their source endophytic fungi and host plants as well as their antitumor activity against various cell lines.

Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 μg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 μg/mL) and decreased the percentage of cells in S (50 μg/mL) and G2/M (50 and 25 μg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.

Context: Bergamot, mainly produced in the Ionian coastal areas of Southern Italy (Calabria), has been used since 1700 for its balsamic and medicinal properties. Phytochemical profiling has confirmed that bergamot juices are rich in flavonoids, including flavone and flavanone glycosides which are responsible for its beneficial effects. Objective: Recently, it was shown that the combination of natural compounds with conventional treatments improves the efficacy of anticancer therapies. Natural compounds with anticancer properties attack cancerous cells without being toxic to healthy cells. Bergamot can induce cytotoxic and apoptotic effects and prevent cell proliferation in various cancer cells. Methods: In this review, the antiproliferative, pro-apoptotic, anti-inflammatory, and antioxidant effects of bergamot are described. Information was compiled from databases such as PubMed, Web of Science, and Google Scholar using the key words ‘bergamot’ accompanied by ‘inflammation’ and, ‘cancer’ for data published from 2015–2021. Results: In vitro and in vivo studies provided evidence that different forms of bergamot (extract, juice, essential oil, and polyphenolic fraction) can affect several mechanisms that lead to anti-proliferative and pro-apoptotic effects that decrease cell growth, as well as anti-inflammatory and antioxidant effects. Conclusions: Considering the effects of bergamot and its new formulations, we affirm the importance of its rational use in humans and illustrate how bergamot can be utilized in clinical applications. Numerous studies evaluated the effect of new bergamot formulations that can affect the absorption and, therefore, the final effects by altering the therapeutic profile of bergamot and enhancing the scientific knowledge of bergamot.

Industrial hemp is characterized by a huge amount of by-products, such as inflorescences, that may represent high-quality sources of biomolecules with pharmaceutical interest. In the present study, we have evaluated the phytochemical profile, including terpene and terpenophenolic compounds, of the essential oils (EOs) of Futura 75, Carmagnola selezionata and Eletta campana hemp varieties. The EOs were also tested for antifungal properties toward Trichophyton mentagrophytes, Trichophyton rubrum, Arthroderma crocatum, Arthroderma quadrifidum, Arthroderma gypseum, Arthroderma curreyi, and Arthroderma insingulare. In parallel, we investigated the inhibitory effects of the EOs against tyrosinase, and the production of prostaglandin E₂ in isolated mouse skin exposed to hydrogen peroxide. In human H1299 lung adenocarcinoma cells, we also evaluated the influence of the EOs on the gene expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are involved in SARS-CoV-2 entry in human host. E-caryophyllene and α-pinene were the prominent terpenes in the EOs, whereas the cannabidiolic acid was the terpenophenol present at higher concentration. The EOs inhibited the growth of all tested dermatophytes species. In isolated skin specimens, EOs prevented the hydrogen-peroxide-induced synthesis of prostaglandin E₂, consistent with the intrinsic antityrosinase activity. Finally, in H1299 cells, all tested EOs reduced the gene expression of ACE-2 and TMPRSS2, as well. Therefore, the present findings highlight the rationale for the use of the present EOs against infectious diseases.

The thymus is the primary organ responsible for de novo generation of immunocompetent T cells that have a diverse repertoire of antigen recognition. During the developmental process, 98% of thymocytes die by apoptosis. Thus apoptosis is a dominant process in the thymus and occurs through either death by neglect or negative selection or through induction by stress/aging. Caspase activation is an essential part of the general apoptosis mechanism, and data suggest that caspases may have a role in negative selection; however, it seems more probable that caspase-8 activation is involved in death by neglect, particularly in glucocorticoid-induced thymocyte apoptosis. Caspase-8 is active in double-positive (DP) thymocytes in vivo and can be activated in vitro in DP thymocytes by T-cell receptor (TCR) crosslinking to induce apoptosis. Caspase-8 is a proapoptotic member of the caspase family and is considered an initiator caspase, which is activated upon stimulation of a death receptor (e.g., Fas), recruitment of the adaptor molecule FADD, and recruitment and subsequent processing of procaspase-8. The main role of caspase-8 seems to be pro-apoptotic and, in this review, we will discuss about the involvement of caspase-8 in (1) TCR-triggered thymic apoptosis; (2) death receptor-mediated thymic apoptosis; and (3) glucocorticoid-induced thymic apoptosis. Regarding TCR triggering, caspase-8 is active in medullary, semi-mature heat-stable antigen^hi (HAS^hi SP) thymocytes as a consequence of strong TCR stimulation. The death receptors Fas, FADD, and FLIP are involved upstream of caspase-8 activation in apoptosis; whereas, Bid and HDAC7 are involved downstream of caspase-8. Finally, caspase-8 is involved in glucocortocoid-induced thymocyte apoptosis through an activation loop with the protein GILZ. GILZ activates caspase-8, promoting GILZ sumoylation and its protection from proteasomal degradation.