Moscatilin (stilbenoid) is a plant-derived anticancer compound, and it has mostly been isolated from threatened wild Dendrobium species. The present study attempts to evaluate the cytotoxicity of Moscatilin on several cancer cell lines through MTT assay. Additionally, it also aims towards estimating and comparing the radiosensitivity, cell-cycle progression, and apoptotic/necrotic effect induced by Moscatilin on different cell lines. The effects of Moscatilin was compared with another significant stilbenoid anticancer agent, Resveratrol (a structural analog of Moscatilin), whose presence has also been reported in Dendrobiums. Considering the threatened nature of this genus, crude extracts of a tropical and epiphytic Dendrobium species, viz., Dendrobium ovatum, prepared from in vitro seedlings were also tested towards cytotoxicity and radiosensitization efficacy. Moscatilin functioned as an effective radiosensitizer at 5 µg/ml along with 1 Gy X-ray and 200 J/m2 UV-C radiations. It was also able to perturb cell cycle both at replicative and post-replicative phases with the aforementioned combination. Moscatilin, in unison with radiation, triggered immunogenic death specifically on cancer cells starting from Pyroptosis, terminating in Necroptosis. Moscatilin, when used singly, could evoke immunogenic cell death. Analyses of Damage-Associated Molecular Patterns released during radiation and Moscatilin treatment would aid in ascertaining the mode of cell death. Moscatilin is a potential radiosensitizer and must be tested for preclinical and clinical trials to combat cancer.

Background Moscatilin is a bibenzyl derivative (stilbenoid), mainly found in Dendrobium species. This plant-derived chemical is a potential cytotoxic anticancer drug that acts against different cancer types. The present study compared the structural interactions of Moscatilin along with five clinically relevant drugs against two target proteins, viz., Anaphase-Promoting Complex subunit 10/Death of Cyclase 1 and Pyruvate Kinase Muscle isozyme M2 in silico. Out of five clinical ligands, four were plant-derived compounds, viz., Resveratrol, Paclitaxel, Shikonin, and Colchicine. The synthetic chemotherapeutic agent, Mitomycin-C, was used as a ligand to compare the mechanistic insights. The objective of the study was to determine the anticancer potency of Moscatilin in silico. Results Moscatilin was found to have an advantage over other drugs of interest due to its structural simplicity and folding bridge connecting the bibenzyl structures. Moscatilin exhibited dual function by exclusively affecting the cancer cells, creating instabilities in biochemical and molecular cascades. Conclusions The study demonstrates that Moscatilin is has a multi-antimetastatic function. Moscatilin interaction with APC10/DOC1 indicated that the drug is involved with post-replicative inhibition, and with PKM2 showed glycolytic pathway inhibition in cancer cells. Moscatilin can function as an effective cell cycle inhibitor. Graphical abstract

The present study is intended to analyze the occurrence of potent, low produce, naturally occurring stilbenes in protoplasts of wild species and hybrids of Dendrobium. The wild species selected for the study was Dendrobium ovatum, endemic to Western Ghats of India. Protoplasts were isolated from leaves and tepal tissues of all the species and were cultured purely to generate homofusants and cross-cultured to raise heterofusants. Phytochemical composition of protoplast culture with atypical and pure microcolonies was performed using mass spectrometry. Enzyme cocktail of 4% pectinase together with 2% cellulase displayed the highest competence for protoplast isolations. Maximum protoplast density of 30.11 × 10/ml was obtained from D. ovatum leaves in 2 h. Subcellular features such as the presence of partially formed cell wall, the position of the nucleus, chloroplast density, colony existence, and integrity of the plasma membrane were analyzed. Among the pure and cross-cultured protoplasts, the number of heterofusants and homofusants formed were enumerated. The spectral feature extraction of the mass spectrometry indicated the presence of five phenolic marker compounds, viz., tristin, confusarin, gigantol, moscatilin, and resveratrol, some of them in pure and others in assorted protoplast cultures raised from Dendrobium leaves and tepals. The study demonstrated that protoplast fusion technique enabled phytochemical assemblage in vitro as stilbenes tend to get restricted either in a tissue or species specific manner. This is the first report showing the presence of resveratrol, moscatilin, tristin, gigantol, and confusarin in wild and hybrid species from cultured Dendrobium protoplasts in vitro.

Moscatilin, a bibenzyl derivative (stilbenoid), mostly found in one of the largest genera of Orchidaceae; Dendrobium has many therapeutic benefits. Its function as an anticancer agent has been widely demonstrated through many research investigations. However, the compound has not been produced in vitro to date. The present study highlights the development of cultures viz., seedling generation, callus induction and callus regeneration (transformation of callus into plantlets). These cultures were devised to conserve the threatened tropical epiphytic orchid species, Dendrobium ovatum and identify their potential towards moscatilin bioproduction in vitro. Among the three culture platforms, callus-derived plantlets could yield high moscatilin when treated with l-Phenylalanine as a precursor. Tissue differentiation was found to be indispensable for the high production of this polyphenol. These cultures also offer potential commercial benefits as they can serve as appropriate platforms to decode moscatilin biosynthesis and other significant bibenzyl derivatives. Elicitors, such as chitosan, salicylic acid, and methyl jasmonate, were found, causing an enhancement in moscatilin content in the cultures. The seedlings obtained can serve towards ecorestoration and preservation of the studied species. Callogenesis was useful in plantlet regeneration, as callus-derived plantlets could be utilized for the enrichment and commercial scale-up of moscatilin-like chemicals.

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