Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent.

Machine learning tools can now help with improving Taxol production in plant cell cultures

Chemotherapeutic intervention for cancer care is an important step. One of the most effective chemotherapy agents in use today is Paclitaxel (PTX), sold under the common name Taxol and Oxanol. Due to its ability to inhibit microtubule formation in cells, PTX is effective at all stages of the cancer and is FDA approved for treatment of many types of cancer (ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer). PTX is a plant alkaloid in the taxane family of compounds obtained from bark of the Pacific Yew tree (Taxus brevifolia) [1]. Adequate market supply of PTX has remained a challenge, as paclitaxel represents only a minor proportion of the total taxoid content of the Taxus species. Over the years, research into finding an alternate to cutting down Yew trees for PTX harvesting has been on the forefront. It is estimated that up to 60 trees may need to be harvested for the treatment of one patient.

Microorganisms: A Potential Source of Bioactive molecules for Antioxidants and Antimicrobial Applications

Oxidative stress is an elevated intracellular level of free oxygen radicals that cause lipid peroxidation, protein denaturation, DNA hydroxylation, and apoptosis, ultimately negotiating cells viability. Antioxidants can scavenge such free radicals, thus reducing the oxidative stress and eventually prevent cellular damage. Medicinal plants, fruits, and spices remain the prioritized sources of antioxidants and antimicrobial properties since the time immemorial, but in contrast to plants, microorganisms can be grown at a faster rate under controlled conditions. They are non-toxic, non-carcinogenic, and biodegradable as compared to synthetic antioxidants. Microorganisms including actinomycetes, archaea, bacteria, protozoa, yeast, and fungi are auspicious source of vital bioactive compounds. The list comprises ample of bioactive components from microorganisms. One of them is bacteriocins, which are ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. It has a great potential as next-generation antibiotics targeting the multiple-drug resistant pathogens. Pneumocandins are antifungal lipohexapeptides derived from the fungus Glarea lozoyensis, and inhibit 1,3-β-glucan synthase of the fungal cell wall and act as a precursor for the synthesis of caspofungin. It is widely used against invasive fungal infections and has been recently approved by the FDA. Taxol (paclitaxel), a chemotherapeutic drug derived from the bark of Taxus brevifolia can also be produced by endophytic fungi Taxomyces andreanae and Nodulisporium sylviforme. It is known to inhibit several fungi such as Pythium, Aphanomyces and Phytophthora. Hispidin and its derivate isolated from P. hispidus, reduce inducible nitric oxide synthase (iNOS) expression, obstruct the transcriptional activity of NF-κB, and also decrease the production of reactive oxygen species (ROS) in macrophages. Astaxanthin, known as an “aquatic” carotenoid produced by H. pluvialis, also has excellent ROS quenching activity. This study mainly focuses on fascinating antioxidant and antimicrobial compounds that have been scarcely investigated in microorganisms and discuss the promise and challenges of microorganisms as providers of health benefits.

Salicylic Acid-Producing Endophytic Bacteria Increase Nicotine Accumulation and Resistance against Wildfire Disease in Tobacco Plants

Endophytic bacteria (EB) are both a novel source of bioactive compounds that confer phytopathogen resistance and inducers of secondary metabolites in host plants. Twenty-seven EB isolated from various parts of Metasequoia glyptostroboides, Ginkgo biloba, Taxus brevifolia, Pinus densiflora, Salix babylonica, and S. chaenomeloides could produce salicylic acid (SA). The highest producers were isolates EB-44 and EB-47, identified as Pseudomonas tremae and Curtobacterium herbarum, respectively. Nicotiana benthamiana grown from EB-44-soaked seeds exhibited a 2.3-fold higher endogenous SA concentration and increased resistance against P. syringae pv. tabaci, the causative agent of tobacco wildfire disease, than plants grown from water-soaked seeds. N benthamiana and N. tabacum grown from EB-44-treated seeds developed 33% and 54% disease lesions, respectively, when infected with P. syringae pv. tabaci, and showed increased height and weight, in addition to 4.6 and 1.4-fold increases in nicotine accumulation, respectively. The results suggest that SA-producing EB-44 can successfully colonize Nicotiana spp., leading to increased endogenous SA production and resistance to tobacco wildfire disease. The newly isolated EB can offer an efficient and eco-friendly solution for controlling wildfire disease and nicotine accumulation in Nicotiana, with additional application for other important crops to increase both productivity and the generation of bioactive compounds.

Chiral Enzymatic Activity in Cell Cultures of Taxus Species

Plant cell suspension cultures of <em>Taxus brevifolia</em> and <em>Taxus globosa</em> were used as biocatalysts on an exogenous racemic substrate in order to determine the influence of several parameters on its configurational deracemization bioactivity. <em>Taxus brevifolia</em> demonstrated a directly proportional relationship between the enantiomeric ratio (er) [1] and the time of reaction, yielding a mixture of 90(<em>S</em>):10(<em>R</em>) after 7 days. Pure enantiomers were tested and the results showed that the (<em>S</em>)-enantiomer remained intact, whereas the (<em>R</em>)-enantiomer was biotransformed. The buffer solution did not present any effect. Sucrose and temperature modified the reaction time and the er. The pH was a critical variable in relation to the age of the suspension cultures. <em>Taxus globosa</em> showed a low efficiency for distinguishing between the enantiomers.