Harnessing Plant Biodiversity for the Discovery of Novel Anticancer Drugs Targeting Microtubules

Abstract

The microtubule cytoskeleton plays a critical role in a wide range of cellular activities and has been shown to be a highly effective target for the treatment of human malignancies. Despite the recent focus on proteomics and high-throughput profiling, it is clear that analysis of plant extracts has yielded several highly efficacious microtubule-targeting agents (MTAs) currently in clinical use, as well as agents in the current pipeline with promising efficacy. To date, a large proportion of the world’s plant biodiversity remains untapped by the pharmaceutical industry, presenting a major opportunity for the discovery of novel pharmacologically active lead compounds. Because plants contain an astonishing array of structurally diverse molecules, they represent an ideal source for the discovery of novel MTA leads. To demonstrate the importance of searching for novel bioactive compounds across the plant kingdom, herein, we summarize the discovery and development of plant-derived MTAs and discuss the challenges associated with searching for novel bioactive compounds from plants. We propose potential solutions to these problems with the aim of facilitating further exploration and identification of novel MTAs from plant biodiversity.

Environmental pollutants damage airway epithelial cell cilia: Implications for the prevention of obstructive lung diseases

“…Cilia can be typically divided into primary nonmotile cilia and motile cilia, depending on the axoneme structure. The axoneme of primary cilia is arranged in a ring of nine peripheral doublet microtubules (termed a 9 + 0 axoneme), and the axoneme of a motile cilium has two single microtubules at the center of the nine peripheral doublet ring (termed a 9 + 2 axoneme) . In addition, the peripheral doublets of motile cilia are attached by inner and outer dynein arms, which allow ciliary movement by ATP‐dependent conformational alterations.…”

Therapeutic targeting of cellular stress responses in cancer

“…Environmental stresses also affect organisms at the cellular level. For example, cancer cells must adapt to both intracellular and extracellular stress, such as hypoxia, starvation, exposure to anticancer drugs, and immune responses . Single‐celled organisms, including bacteria and yeast, have developed mechanisms to survive in the face of environmental stresses by promoting mutagenesis, thereby increasing genetic diversity .…”

Aberrant regulation of autophagy in mammalian diseases

“…Defects in autophagy can lead to many serious pathological disorders, such as cancer [16], immunity and inflammation, neurodegenerative disease and heart diseases (table 1).…”