Résumé
A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.
Résumé
Cancer is a leading cause of death worldwide. Although high cure rates are achievable with current available drugs, this is not without side effects. Hence, attention has been shifted to alternative anticancer agents coming from natural products as treatment options. Extracts from marine sea cucumbers have been investigated for such properties. Frondoside A is a natural glycoside extracted from the sea cucumber, Cucumaria frondosa, which has been used as a traditional remedy, recently, the extract was found to have potential anti-tumor properties. This narrative review aimed at critically analyzing and summarizing the literature available regarding Frondoside A anticancer properties. For that, scientific databases such as PubMed, EMBASE, and ScienceDirect were searched for the keywords; Frondoside A, cancer, metastasis, anticancer properties, and sea cucumbers. Articles in languages other than English were excluded from the study. Such review will help researchers to better tailor future experiments and will enrich the knowledge about natural compounds consumed as traditional substances.
Résumé
An overwhelming body of research has now firmly established that the dietary intake of berry fruits has a positive and profound impact on human health, performance, and disease. Evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. Studies show that the anticancer effects of berry bioactives reduce and repair damage resulting from oxidative stress and inflammation. In addition, also regulate carcinogen and xenobiotic metabolizing enzymes, various transcriptions and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and consumption may provide protection from therapy-associated toxicities. This paper is a comprehensive review of the effects of phytochemicals present in berry fruits on cancer and encompasses the occurrence and bioavailability of these compounds evidences for their effects on the various mechanisms by which may exert their effects. These include effects on cellular differentiation and apoptosis; effects on proteins and enzymes that are involved in these processes at a molecular level, and other various effects through altered immune function and chemical metabolism.