Mitosis-Targeting Natural Products for Cancer Prevention and Therapy

Abstract

Mitosis is a complex process resulting in division of a cell into two daughter cells, and its failure often results in the death of the daughter cells (via apoptotic, necrotic, or proliferative/senescent death). Many chemicals that inhibit the mitotic process (anti-mitotic drugs) have proven effective for killing cancer cells in vitro and in clinical settings. Among the most studied anti-mitotic drugs are plant-origin natural products including taxanes (e.g. paclitaxel, docetaxel) and vinca alkaloids (e.g. vincristine, vinblastine), whose validated target is the spindle microtubules. With the success of these agents, efforts have been made to develop other spindle poisons as well as to improve efficacy of existing spindle poisons with structural modifications. Novel drugs and natural products that inhibit other proteins involved in mitosis (nonmicrotubule targets) have been sought in hopes of expanding available cancer-directed therapies. Recently, significant advances have been made in the understanding of mitotic mechanisms in tumor cells as well as in normal epithelial cells. These advances help us to identify and develop potential natural agents for the prevention and treatment of cancer. This review will focus on natural products that target mitotic process and/or proteins involved in mitotic progression.

Apoptosis Induction byPolygonum minusIs Related to Antioxidant Capacity, Alterations in Expression of Apoptotic-Related Genes, and S-Phase Cell Cycle Arrest in HepG2 Cell Line

“…Luteolin exhibited antiangiogenesis effect by suppressing vascular endothelial growth factor and matrix metalloproteases and was antimetastasis through inhibition of tumor necrosis factor and interleukin-6 which regulate cell migration and metastasis [39]. Besides exhibiting similar mechanisms of action as flavonoids, alkaloids and saponins may also contribute to antiproliferative effects by inducing cell cancer autophagy and antimultidrug resistance and antimitotic effect [40]. Existing data on concomitant use of antioxidant compounds and chemotherapy showed that antioxidant supplementation led to improvement in treatment outcomes, increased survival times, increased tumor response, and reduced toxicity [41].…”

Natural Compounds as Modulators of Cell Cycle Arrest: Application for Anticancer Chemotherapies

“…Since uncontrolled and rapid cell division is a hallmark of cancer, unraveling the molecular mechanisms underlying mitosis is key to understanding how various natural compounds might function as antimitotic agents [8, 10-12]. Many natural compounds that inhibit the mitotic process (antimitotic drugs) have proven effective for killing cancer cells in vitro, in vivo and in clinical settings [8, 10-12]. Among the most studied antimitotic drugs are natural compounds including taxanes (e.g.…”

“…taxol, paclitaxel, docetaxel) and vinca alkaloids (e.g. vincristine, vinblastine), whose validated targets are the spindle microtubules, as reviewed elsewhere [8, 13-18]. Natural compounds, including vinca alkaloids, were shown to induce cell cycle arrest in mitosis associated with aberrant mitotic spindles, while colchicine was found to exhibit the activities leading to blocking of mitosis, as indicated in [8, 13, 14].…”

“…vincristine, vinblastine), whose validated targets are the spindle microtubules, as reviewed elsewhere [8, 13-18]. Natural compounds, including vinca alkaloids, were shown to induce cell cycle arrest in mitosis associated with aberrant mitotic spindles, while colchicine was found to exhibit the activities leading to blocking of mitosis, as indicated in [8, 13, 14]. Both vincristine and vinblastine were found to inhibit the tumor cell proliferation, and display remarkable efficacy in the treatment of testicular cancer, Hodgkin’s lymphoma and acute lymphocytic leukemia, as reviewed in [8, 13-18].…”

“…Novel drugs and natural compounds that inhibit other proteins involved in mitosis (non-microtubule targets) have been sought in hopes of expanding available cancer-directed therapies [8]. Significant advances made in the understanding of molecular mechanisms underlying the cell cycle regulation using the chemotherapeutic agents are of a great importance for improving the efficacy of targeted therapeutics and overcoming resistance to anticancer drugs, especially of natural origin, which inhibit the activities of cyclins and cyclin-dependent kinases (CDKs), as well as other proteins and enzymes involved in proper regulation of cell cycle leading to controlled cell proliferation, as reviewed in [8, 19].…”