Md. Asaduzzaman Khan

Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer.

The epithelial to mesenchymal transition (EMT) is an important step for the developmental process. Recent evidences support that EMT allows the tumor cells to acquire invasive properties and to develop metastatic growth characteristics. Some of the transcription factors, which are actively involved in EMT process, have a significant role in the EMT–metastasis linkage. A number of studies have reported that EMT-inducing transcription factors (EMT-TFs), such as Twist, Snail, Slug, and Zeb, are directly or indirectly involved in cancer cell metastasis through a different signaling cascades, including the Akt, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK) and Wnt pathways, with the ultimate consequence of the downregulation of E-cadherin and upregulation of metastatic proteins, such as N-cadherin, vimentin, matrix metalloproteinase (MMP)-2, etc. This review summarizes the update information on the association of EMT-TFs with cancer metastasis and the possible cancer therapeutics via targeting the EMT-TFs.

Anticancer activities of Nigella sativa (black cumin).

Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves bodys defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2∼3 decades. There are not so many research works done with this important traditional medicine and very few reports exist in the scientific database. In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms.

Genetic polymorphisms of metabolic enzymes—CYP1A1, CYP2D6, GSTM1, and GSTT1, and gastric carcinoma susceptibility

Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. In this study, the relationships between genetic polymorphisms of phase I metabolic enzymes including cytochrome P450 1A1 (CYP1A1), CYP2D6 and phase II metabolic enzymes such as glutathione S-transferase M1 (GSTM1) and GSTT1 and gastric carcinoma susceptibility were investigated. Genomic DNA was isolated from the peripheral blood of 129 healthy controls and 123 gastric carcinoma patients from Han ethnic group of Hunan Province located in Central South China. The genetic polymorphisms of the above mentioned enzymes were analyzed using PCR-RFLP techniques. There was no significant difference among the frequencies of CYP1A1 and/or CYP2D6 gene’s wild type, heterozygous or homozygous mutations between the gastric carcinoma group and control group. But the differences among the frequencies of GSTM1 and GSTT1 null genotype between the gastric carcinoma and control group were significant (both P < 0.05). Also there were significant differences in the frequencies of GSTM1 null in high/high–middle differentiated, middle differentiated, middle–low differentiated and low differentiated gastric tumor separately. GSTM1 null showed an increased risk in middle–low differentiated and low differentiated gastric carcinoma type, but GSTT1 null was not a risk factor for the four pathological types of gastric carcinoma mentioned above. We report here that the genotypes of CYP1A1 and CYP2D6 are not associated with gastric carcinoma risk; GSTM1 null, but not GSTT1 null inheritably increases risk of some pathological types of gastric carcinoma in Han ethnic population of Hunan Province.

Nutritional and Medicinal Importance of Pleurotus Mushrooms: An Overview

Mushrooms of Pleurotus genus are popularly consumed all over the world due to their taste, flavor, high nutritional values, and some medicinal properties. Several species of this genus are rich in proteins with essential amino acids, physiologically important polysaccharides and essential fatty acids, dietary fibers, important minerals, and some vitamins. Because of these nutritional composition and the presence of some other active ingredients, these mushrooms have been reported to have anticancer, antihypercholesterolemic, antihypertensive, antidiabetic, antiobesity, hepatoprotective, antiaging, antimicrobial, antiallergic, and antioxidant activities. The high nutritional value and potential medicinal uses suggest that the Pleurotus mushrooms are important functional foods or nutraceuticals.

Hericium erinaceus: an edible mushroom with medicinal values

Abstract Mushrooms are considered as nutritionally functional foods and source of physiologically beneficial medicines. Hericium erinaceus, also known as Lion’s Mane Mushroom or Hedgehog Mushroom, is an edible fungus, which has a long history of usage in traditional Chinese medicine. This mushroom is rich in some physiologically important components, especially β-glucan polysaccharides, which are responsible for anti-cancer, immuno-modulating, hypolipidemic, antioxidant and neuro-protective activities of this mushroom. H. erinaceus has also been reported to have anti-microbial, anti-hypertensive, anti-diabetic, wound healing properties among other therapeutic potentials. This review article has overviewed the recent advances in the research and study on H. erinaceus and discussed the potential health beneficial activities of this mushroom, with the recognition of bioactive compounds responsible for these medicinal properties.

Cultivation of different strains of king oyster mushroom (Pleurotus eryngii) on saw dust and rice straw in Bangladesh.

Pleurotus eryngii is a popular mushroom due to its excellent consistency of cap and stem, culinary qualities and longer shelf life. In Bangladesh, where Pleurotus mushrooms are very popular, P. eryngii may take position among the consumers, but currently this mushroom is not cultivated in large scale there. In this study, 3 strains of P. eryngii such as Pe-1 (native to Bangladesh), Pe-2 (germplasm collected from China) and Pe-3 (germplasm collected from Japan) were cultivated on saw dust and rice straw and their growth and yield parameters were investigated. Pe-1 on saw dust showed the highest biological yield and efficiency (73.5%) than other strains. Also, the mycelium run rate and number of fruiting bodies were higher in Pe-1 than other two strains. The quality of mushroom strains was near about similar. On saw dust, the yield and efficiency were better than those cultivated on rice straw, however, on straw; the mushroom fruiting bodies were larger in size. This study shows the prospects of P. eryngii cultivation in Bangladesh and suggests further study in controlled environment for higher yield and production.

Polymorphisms of DNA repair genes XPD , XRCC1 , and OGG1 , and lung adenocarcinoma susceptibility in Chinese population

Lung adenocarcinoma (ADC) is one of the major histological types of lung cancer. Genetic polymorphism in DNA repair genes and lung ADC susceptibility is well documented. In this case–control study, the association between the polymorphic sites of DNA repair genes XPD-751, XRCC1-399, and OGG1-326, and lung ADC susceptibility in ethnic Han Chinese population has been investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 82 lung ADC patients from the people of Hunan Province, China. Polymorphisms of the investigated genes were analyzed by using polymerase chain reaction–restriction fragment length polymorphism. There was no significant difference between the samples from lung ADC patients and healthy controls about the genotype frequencies of XPD-751, XRCC1-399, and OGG1-326 sites. However, multifactor dimensionality reduction analysis showed that the genetic polymorphisms of the three-loci models of DNA repair genes (XPD-751/XRCC1-399/OGG1-326) are associated with lung ADC. Thus, this study reveals that a three-order interaction among the polymorphic sites of XPD-751, XRCC1-399, and OGG1-326 is associated with lung ADC risk in the studied population, although polymorphism in individual gene was not associated.

Autotaxin: a protein with two faces.

Autotaxin (ATX) is a catalytic protein, which possesses lysophospholipase D activity, and thus involved in cellular membrane lipid metabolism and remodeling. Primarily, ATX was thought as a culprit protein for cancer, which potently stimulates cancer cell proliferation and tumor cell motility, augments the tumorigenicity and induces angiogenic responses. The product of ATX catalyzed reaction, lysophosphatidic acid (LPA) is a potent mitogen, which facilitates cell proliferation and migration, neurite retraction, platelet aggregation, smooth muscle contraction, actin stress formation and cytokine and chemokine secretion. In addition to LPA formation, later ATX has been found to catalyze the formation of cyclic phosphatidic acid (cPA), which have antitumor role by antimitogenic regulation of cell cycle, inhibition of cancer invasion and metastasis. Furthermore, the very attractive information to the scientists is that the LPA/cPA formation can be altered at different physiological conditions. Thus the dual role of ATX with the scope of product manipulation has made ATX a novel target for cancer treatment.

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics.Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics.

MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets and functional effects of miR-34a on epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT-inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is downregulated in human metastatic breast cancers (MBC) compared to normal breast tissues and is negatively correlated with clinicopathological features of MBC patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly inhibits cell migration and invasion, but exhibits no clear effect on BC cell growth. We found that miR-34a is able to inactivate EMT signaling pathway with mediatory of NOTCH1, TWIST1, and ZEB1 upon 3′-UTR activity in MBC cell lines, but has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in BT-549 cell line, indicating that they might be a promising therapeutic combination against breast cancer metastasis. Epigenetic inactivation of the EMT-TFs/miR-34a pathway can potentially alter the equilibrium of these regulations, facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR-34a alone could serve as a potential therapeutic agent for MBC, and together with TQ, their therapeutic potential is synergistically enhanced.