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ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000035
Noscapinoids: A new Class of Anti-Cancer Drugs Demand
Biotechnological Intervention
Harish C. Joshi
Emory University, School of Medicine, Department of Cell Biology, GA, USA
M
icrotubules (MTs) are cytoskeletal components that play a critical role in many
cellular processes such as maintenance of cell shape and polarity, intracellular
transport of vesicles and organelles, and cellular motility. During cell division, MTs
form a bipolar microtubule (MT) array, called the mitotic spindle responsible for the
accurate distribution of chromosomes into two daughter cells. MTs are assembled
from alpha- and beta-tubulin heterodimers, and are highly dynamic structures
that alternate between periods of growth and shortening. This dynamic instability
property is crucial for MTs to carry out many of their cellular functions. Disruption
of MT dynamics can lead to the formation of abnormal mitotic spindles, thereby
preventing the normal cell proliferation. The critical role that MTs play in cell division
makes them a very suitable target for the development of chemotherapeutic drugs
against the rapidly dividing cancer cells. The effectiveness of MT-targeting drugs
has been validated by the successful use of several vinca alkaloids and taxanes
for the treatment of a wide variety of human cancers. These agents inhibit or
promote the polymerization of tubulin respectively, halt mitosis of rapidly dividing
cells, induce apoptosis, and are reasonably effective in cancer chemotherapy. As a
testament to this, USFDA has approved the use of taxanes such as paclitaxel and
taxotere as a first line chemotherapy for ovarian and breast cancers and vincas
such as vinblastine, vincristine, and vinorelbine for some hematological pathologies.
However, drug resistance is a common problem with repeated and prolonged
administration of these agents, possibly owing to the amplification of a membrane
glycoprotein involved in efflux of the drug. Moreover, these anti-MT agents are
frequently toxic to normal tissues and are effective only for certain types of cancers.
Despite the current cumbersome intravenous slow infusions, requiring multiple
hospital visits, uncomfortable side effects of the gastro intestinal and immune
systems, neutrocytopenia, and peripheral neuropathies, the first generation MT
drugs, vincas, taxanes, epothilones, have proven that MTs are valuable targets for
anti-cancer therapy. Noscapine and its promising derivatives now offer the prospect
of a nicer, kinder, and gentler opium derived non-narcotic oral safe class of anti-
cancer drugs that can be taken at home. Noscapine has already begun its progress
into the pipeline of clinical drug development. New more effective and even targeted
derivatives are under development in our group, and we hope many more will follow
suite. In addition, biotechnological interventions are underway to obtain improved
production of the compound and efforts to metabolically engineer the biosynthetic
pathways for enhancing yield. Another challenge these useful drugs face, is their
poor solubility in biocompatible solvents. As a result they are solubilized in unfriendly
carriers such as Cremphor EL that runs the risk of anaphylactic shocks and medical
emergencies. Hence, there is an urgent need for new and better chemotherapeutic
drugs for cancer treatment.
ANALBIOANAL-2010
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