Withaferin A (WA) is present abundantly in Withania somnifera, a well-known Indian medicinal plant. Here we demonstrate how WA exhibits a strong growth-inhibitory effect on several human leukemic cell lines and on primary cells from patients with lymphoblastic and myeloid leukemia in a dose-dependent manner, showing no toxicity on normal human lymphocytes and primitive hematopoietic progenitor cells. WA-mediated decrease in cell viability was observed through apoptosis as demonstrated by externalization of phosphatidylserine, a time-dependent increase in Bax/Bcl-2 ratio; loss of mitochondrial transmembrane potential, cytochrome c release, caspases 9 and 3 activation; and accumulation of cells in sub-G0 region based on DNA fragmentation. A search for the downstream pathway further reveals that WA-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2 and HSP27 in leukemic cells. The RNA interference of p38MAPK protected these cells from WA-induced apoptosis. The RNAi knockdown of p38MAPK inhibited active phosphorylation of p38MAPK, Bax expression, activation of caspase 3 and increase in Annexin V positivity. Altogether, these findings suggest that p38MAPK in leukemic cells promotes WA-induced apoptosis. WA caused increased levels of Bax in response to MAPK signaling, which resulted in the initiation of mitochondrial death cascade, and therefore it holds promise as a new, alternative, inexpensive chemotherapeutic agent for the treatment of patients with leukemia of both lymphoid and myeloid origin.

Natural products are important sources of anti-cancer lead molecules. Many successful anti-cancer drugs are natural products or their analogues. Many more are under clinical trials. The present review focuses on chemopreventive and anti-cancer activities of polar and non-polar extracts, semi purified fractions and pure molecules from terrestrial plants of India reported between 2005 and 2010 emphasizing possible mechanisms of action of pure molecules.

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The literature contains several reviews on lectins in general, covering mainly those from plants and invertebrates. However, the sialic acid binding lectins have not been reviewed so far. Considering the importance of sialic acids in cell sociology, lectins which specifically recognize terminal sialic acid residues are potentially useful as analytical tools in studying the biological functions of sialoglycoconjugates. These lectins, along with monoclonal antibodies raised against sialoglycoconjugates, have been used in the detection, affinity purification, cytochemical localization and quantitation of such glycoconjugates. In this review the main emphasis has been placed on the occurrence, general purification procedures, macromolecular properties, sugar specificities and applications of these lectins.

PA is an opportunistic pathogen that is commonly associated with severe infection in immunocompromised hosts. Siglec-9 binds with Sias by cis interaction on the neutrophil surface, thereby reducing immunological activity. However, neutrophils bind with pathogens through trans interactions of siglec-9 with Sias. Neutrophils kill invading pathogens by NETs, along with extracellular phagocytosis. Here, we report the mode of the adsorption of Sias by PA from host serum, the interaction of PA(+Sias) with human neutrophils, and the resulting neutrophil immunological activity. The α2-3-linked sialoglycoproteins adsorbed by PA exhibited potent binding with the soluble siglec-9-Fc chimeras, CHO-siglec-9 and siglec-9 on neutrophils. The binding between PA(+Sias) and neutrophils was blocked by the synthetic sialoglycan Neu5Acα2-3Galβ1-4GlcNAc, confirming the linkage-specific, Sias-siglec-9 interaction. The PA(+Sias) and siglec-9 interaction on neutrophils reduced the level of ROS and the release of elastase, resulting in a reduction of NETs formation, demonstrating the role of the sialoglycoproteins adsorbed by PA in the weakening of neutrophil activity. The resistance of PA(+Sias) to NETs was made evident by the increased survival of PA(+Sias). Moreover, the decrease in PA(-Sias) survival demonstrated the involvement of NETs formation in the absence of the Sias-siglec-9 interaction. N-actylcysteine or sivelestat-pretreated neutrophils enhanced the survival of PA(-Sias). DNAse-pretreated neutrophils did not exhibit any NETs formation, resulting in the enhanced escape of PA(-Sias). Taken together, one of the survival mechanisms of PA(+Sias) is the diminution of innate immunity via its adsorption of sialoglycoproteins by its engagement of the inhibitory molecule siglec-9. This is possibly a general mechanism for pathogens that cannot synthesize Sias to subvert immunity.