Chronic myeloid leukemia (CML) is a hematological malignancy that arises due to reciprocal translocation of 3′ sequences from c-Abelson (abl) protooncogene on chromosome 9 with 5′ sequence of truncated break point cluster region (bcr) to chromosome 22. The fusion gene product BCR-ABL, a functional oncoprotein p210, is a constitutively activated tyrosine kinase that activates several cell proliferative signaling pathways. BCR-ABL-specific tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib and ponatinib potently inhibit CML progression. However, drug resistance owing to BCR-ABL mutations and overexpression is still an issue. Natural products are chemical compounds or substances produced by living organisms. They are becoming an important research area for cancer drug discovery due to their low toxicity and cost-effectiveness. Several lines of evidence show that many NPs such as alkaloids, flavonoids, terpenoids, polyketides, lignans and saponins inhibit CML cell proliferation and induce apoptosis. NPs not only differentiate CML cells into monocyte/erythroid lineage but also can reverse the multi-drug resistance (MDR) in CML cells. In this chapter, we review the anti-CML activity of various NPs.
Part of the book: Anti-cancer Drugs