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Information Seminar Paper

Title

RECENT PROGRESS IN ANTI-TUMOR ACTIVITY OF NOSCAPINE

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Abstract

 Introduction: Noscapine is an isoquinoline alkaloide found in opium latex. This compound is devoid of any significant analgesic, sedative or euphoriant associated with this group of compounds. While this is an old drug, the only important clinical effect associated with noscapine is its antitussive activity. However, current discovery by Joshi's team showed its anti-tumor activity led to considerable interest. Noscapine shows few side effect and its water solubility and feasibility for oral administration are valuable advantage over other anti-tumor agents. Furthermore, noscapine did not inhibit primary immune responses, which limits use of other chemotherapeutic agents in the treatment of human cancer. Unlike other anti-microtubule drugs, it has low toxicity and high aqueous solubility. It must be said that anti-microtubule drugs have been hampered by development of drug resistance. Noscapine can effectively reverse the resistance to various drugs such as vincristine, doxyrubicin, etc.Methods: The molecular mechanism of its apoptotic activity was studied. Apoptotic effects of noscapine on two myeloid cell lines, apoptosis-proficient HL60 cells and apoptosis-resistant K562 cells, were analyzed.Results: Noscapine can effectively inhibit the proliferation and cell death in both drug-sensitive and drug- resistant human cell lines. Increase in caspases-2,-3,-6,-8 and -9 activities, PARP cleavage, and DNA fragmentation suggested the induction of apoptosis. Noscapine increased the Bax/Bcl-2 ratio with significant decrease of Bcl-2 expression accompanied with Bcl-2 phosphorylation. Analysis of activation of the caspase cascade involved in the noscapine-induced apoptosis was performed using inhibitory approach. Since the Fas-null K562 cells were selected for this analysis, activation of caspase-8 in Fas-independent manner and downstream of caspase-9 is suggested.Conclusion: noscapine has great potential as a new anti cancer drug.

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