This review chronicles the exploration of the curcumin in terms of development of analogues for the anticancer activity over the last century. Curcumin is a natural phytochemical obtained from dried root and rhizome of Turmeric (Curcuma Longa). It has been shown to interfere with multiple cell signaling pathways, including apoptosis (activation of caspases and downregulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), angiogenesis (VEGF), and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). In the last decade it has been much explored and various synthetic analogues have been prepared and evaluated for various pharmacological activities. Most of the analogues have shown very good anticancer activity in various models and various cell lines. However, some analogues have also shown antioxidant, anti-HIV, antimutagenic, antiangiogenic, antimalarial, antitubercular, antiandrogenic, COX inhibitory activities. Few analogues have shown very potent results and may be considered as clinical candidates for the development of future anticancer agent. This review contains 728 curcumin analogues and covers the literature from 1815 to mid 2009 and 93 references are cited.
Developing stable Chinese hamster ovary (CHO) cell lines for biotherapeutics is an irreversible process and therefore, key quality attributes, such as sequence variants, must be closely monitored during cell line development (CLD) to avoid delay in the developmental timeline, and more importantly, to assure product safety and efficacy. Sequence variants, defined as unintended amino acid substitution in recombinant protein primary structure, result from alteration at either the DNA or the protein level. Here, for the first time, we report the application of transcriptome sequencing (RNAseq) in an IgG1 monoclonal antibody (mAb) CLD campaign to detect, identify, and eliminate cell lines containing low-level point mutations in recombinant coding sequence. Among the top eleven mAb producers chosen from transfectant, clone or subclone stages, three of the cell lines contained either missense or nonsense point mutations at a low level of less than 2%. Subsequent LC/MS/MS characterization detected ∼3% sequence variants with an amino acid change from Ser to Leu at residue 117 in the heavy chain of transfectants 11 and 27. This substitution is consistent with the RNAseq finding of a C/T mutation located at 407 base pair (TCA→TTA) in the heavy chain coding sequence. Here we demonstrate that RNAseq is a rapid and highly sensitive method to identify low-level genetic mutation de novo corresponding to the amino acid substitution that elicits sequence variant(s). Its implementation in CLD constitutes an early and effective step in identifying desired CHO expression cell lines.
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