Current Pharmaceutical Design - Volume 25, Issue 8, 2019

Cancer hallmarks help in understanding the diversity of various neoplasms. Epithelial cancers play an immense role in the tumor biology through Epithelial-Mesenchymal Transition (EMT) process. Receptor tyrosine kinase, as well as phosphatidyl ionositol-3 kinase pathways, play an important role in the regulation of cell proliferation, survival, and differentiation during EMT. Till date, numerous studies have shown modulation in the expression profile of potential targets like CD44, EGFR, and Rac in epithelial cancers. CD44 interacts with EGFR and recruits other molecules which further activate the Rac pathway intermediates. This review mainly focused on modulation of genes like CD44, EGFR, and Rac pathway intermediates which play a crucial role in the tumor progression, metastasis, proliferation, and invasion characteristics in epithelial cancers with EMT properties. Hence, targeting Rac pathway might be a more strategically relevant approach in treating epithelial cancers.

Heat shock protein 90 (Hsp90) plays an essential role in various physiological and pathological processes. It activates client proteins to participate in tumor progression. Blocking Hsp90 could enable effective antitumor effects in many tumor types, such as multiple myeloma and colon cancer. Recently, it has motivated an interest in Hsp90 inhibitors that bind to the N-terminal or C-terminal ATP pocket as antitumor drugs. We reviewed the data from experimental and clinical trials on Hsp90 inhibitors in the treatment of different malignancies to explore and summarize their antitumor mechanisms.

Background: Ovarian cancer is the most malignant tumor in gynecological tumors, with low five-year survival rate. The main reasons are diagnosis at advanced stages (the early symptoms are uncharacteristic, and most are diagnosedlate.), relapse, and resistance to existing chemotherapy drugs. Methods: Search strategy was performed in the following steps. Firstly, LncRNA related to ovarian cancer was retrieved by using the LncRNA Disease database, and articles were searched by searching keywords: ovarian cancer, drug resistance, and LncRNA retrieved from the LncRNA Disease database. Results/Conclusion: With the development of the study on drug resistance of ovarian cancer, the role of LncRNAs as sensitive biomarker and therapeutic target has emerged, providing a direction for precision medicine of ovarian cancer resistance.

Background and objective: Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors. Methods: Mice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated. Results: The growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration. Conclusion: This study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ.

Ethnopharmacological relevance: The genus Curcuma, which is the most important source of curcumin, has been widely used in different traditional medicines. Various species of Curcuma have long been used for several purposes such as healing wounds, liver disorders, jaundice and also as a blood purifier. Aim of the study: This review focused on the ethnopharmacological uses and phytochemical aspects of Curcuma. Additionally, in this study, the different properties of two species of Curcuma in Islamic Traditional Medicine (ITM), C. longa and C. zedoaria, as well as their pharmacological aspects in modern medicine are reviewed. Materials and methods: ITM literatures were searched to find Curcuma’s applications. Also, electronic databases including PubMed and Scopus were searched to obtain studies giving any in vitro, in vivo or human evidence of the efficacy of C. longa and C. zedoaria in the treatment of different diseases. ChemOffice software was used to find chemical structures. Results: The analysis showed that ethno-medical uses of Curcuma have been recorded for centuries. Approximately, 427 chemical compounds have been isolated and identified from Curcuma spp. This genus is rich in flavonoids, tannins, anthocyanin, phenolic compounds, oil, organic acids and inorganic compounds. Curcumin is one of the main active ingredients in Curcuma which has strong anti-inflammatory and antioxidant effects. Besides, pharmacological studies have indicated wide range of Curcuma’s activities, such as hepato-protective, antifungal, antihypertensive and neuroprotective. Conclusions: In this study, we reviewed various studies conducted on ethno-medicinal, ITM properties and photochemistry of Curcuma spp. Also, pharmacological activities of two species, C. longa and C. zedoaria are summarized. Pre-clinical investigations have demonstrated some of the traditional aspects of Curcuma, such as wound healing, anti-arthritic, anti-tumor and liver protective activities. These could be related to antioxidant and anti-inflammatory properties of Curcuma which might be due to high amounts of phenolic compounds. Curcuma is mentioned to have neural tonic properties in ITM which have been confirmed by some animal studies. Considering various preclinical studies on C. longa and C. zedoaria and their active ingredient, curcumin, randomized controlled trials are warranted to confirm their promise as a clinically effective hepato and neuro-protective agents.