2,2′-Diphenyl-3,3′-Diindolylmethane: A Potent Compound Induces Apoptosis in Breast Cancer Cells by Inhibiting EGFR Pathway

Despite recent advances in medicine, 30–40% of patients with breast cancer show recurrence underscoring the need for improved effective therapy. In this study, by in vitro screening we have selected a novel synthetic indole derivative 2,2''-diphenyl-3,3''-diindolylmethane (DPDIM) as a potential anti- breast cancer agent. DPDIM induces apoptosis both in vitro in breast cancer cells MCF7, MDA-MB 231 and MDA-MB 468 and in vivo in 7,12-dimethylbenz[α]anthracene (DMBA) induced Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show that DPDIM exerts apoptotic effect by negatively regulating the activity of EGFR and its downstream molecules like STAT3, AKT and ERK1/2 which are involved in the proliferation and survival of these cancer cells. In silico predictions also suggest that DPDIM may bind to EGFR at its ATP binding site. DPDIM furthermore inhibits EGF induced increased cell viability. We have also shown decreased expression of pro-survival factor Bcl-XL as well as increase in the level of pro-apoptotic proteins like Bax, Bad, Bim in DPDIM treated cells in vitro and in vivo. Our results further indicate that the DPDIM induced apoptosis is mediated through mitochondrial apoptotic pathway involving the caspase-cascade. To the best of our knowledge this is the first report of DPDIM for its anticancer activity. Altogether this report suggests that DPDIM could be an effective therapeutic agent for breast cancer.     

Physiological role of rice germin-like protein 1 (OsGLP1) at early stages of growth and development in <Emphasis Type="Italic">indica</Emphasis> rice cultivar under salt stress condition

Since their discovery, germin and germin-like proteins (GLPs) were found to be associated with salt stress along with other physiological roles. Although a number of GLP family members showed spatio-temporal changes in expressional up-regulation or down-regulation upon exposure to salt stress across plant species, very little is known about any rice GLP member in relation to salt stress. Rice germin-like protein 1 (OsGLP1), belongs to “Cupin” superfamily, is a plant glycoprotein and is associated with the plant cell wall. Our previous studies on endogenous down-regulation of OsGLP1 in rice and heterologous expression in tobacco documented that the OsGLP1 possessing superoxide dismutase activity is involved in cell wall cross-linking and fungal disease resistance in plants. In the present study, the transgenic rice lines having reduced OsGLP1 expression were analyzed in advanced generation for deciphering the involvement of OsGLP1 under salt stress. OsGLP1 gene-silencing construct integated transgenic lines were confirmed by Southern hybridization and RNA-interfernce (RNAi) mediated gene-silencing of the transgenic rice lines was confirmed by northern blot analysis. The expression of endogenous OsGLP1 protein level was found to be reduced in salt sensitive indica rice cultivar Badshahbhog following salt stress. Additionally, the RNAi-mediated OsGLP1 gene-silencing in transgenic rice lines resulted improved salt tolerance as compared to the untransformed ones during seed germination, initial establishment, early seedling growth and callus proliferation. Salt tolerance nature of the OsGLP1 gene-silenced plants at early stages of growth and development depicted the negative correlation between the OsGLP1 expression and salt tolerance of rice.     

The FKBP families of higher plants: Exploring the structures and functions of protein interaction specialists

The FK506-binding proteins (FKBPs) are known both as the receptors for immunosuppressant drugs and as prolyl isomerase (PPIase) enzymes that catalyse rotation of prolyl bonds. FKBPs are characterised by the inclusion of at least one FK506-binding domain (FKBd), the receptor site for proline and the active site for PPIase catalysis. The FKBPs form large and diverse families in most organisms, with the largest FKBP families occurring in higher plants. Plant FKBPs are molecular chaperones that interact with specific protein partners to regulate a diversity of cellular processes. Recent studies have found that plant FKBPs operate in intricate and coordinated mechanisms for regulating stress response and development processes, and discoveries of new interaction partners expand their cellular influences to gene expression and photosynthetic adaptations. This review presents an examination of the molecular and structural features and functional roles of the higher plant FKBP family within the context of these recent findings, and discusses the significance of domain conservation and variation for the development of a diverse, versatile and complex chaperone family.     

Intense Floral Scent Emission in Polianthes tuberosa L. (Tuberose) Variants Sprouted from γ-Irradiated Tubers

Journal of Plant Growth Regulation - Tuberose (Polianthes tuberosa L.) is a tuberous, perennial, night-blooming ornamental plant which is commercially cultivated in different parts of India. In the...     

Isolation and characterization of three phosphoamido-neomycins and their conversion into neomycin by Streptomyces fradiae

Some amino acids, particularly glycine and serine, favour the accumulation in the fermentation broth of three phosphorylated amino sugar compounds that are intermediates in the pathway of neomycin biosynthesis by Streptomyces fradiae 3535. The compounds were separated and purified further by Amberlite IRC-50 (NH(4) (+) form). The intermediates were characterized by physicochemical methods as neomycin B pyrophosphate (C(23)H(48)N(6)O(19)P(2),3H(2)O), neomycin C pyrophosphate (C(23)H(48)N(6)O(19)P(2),3H(2)O) and neomycin C dipyrophosphate complex (C(24)H(66)N(8)O(33)P(4)).     

Mechanisms of EBV-mediated oncogenesis

Epstein-Barr virus (EBV) is the DNA tumor virus, which is known to be relevant to various cancers. EBV maintains latent infection in cancer cells, and there are three types of latent infection (type I-III) according to the patterns of viral latent genes expression. EBV has the ability to transform B cells into immortalized lymphoblastoid cell lines (LCL) showing type III latency, in which all latent genes are expressed. The mechanism of B-cell transformation has provided a model of EBV-associated lymphomas in immunosuppressed individuals. In type I and II latency, the limited numbers of latent genes are expressed. Previous studies have demonstrated the oncogenic functions of latent EBV genes including nuclear antigen EBNA1, membrane protein LMP1 and LMP2A. In addition, we have demonstrated that EBV-encoded small RNA EBERs play a significant role in oncogenesis. Here we summarize recent progresses in the studies on molecular mechanisms of EBV-mediated oncogenesis.