Current Drug Metabolism - Volume 20, Issue 12, 2019

One of the major challenges currently facing cancer therapy is the development of drug resistance either intrinsically or as a result of treatment. Treatment evasion is mediated by an intricate web of signalling cascades and adaptations caused by selective therapeutic pressure, leading to metastatic spread and patient death. Hence, discovering and designing novel therapeutic compounds and regimens based on specific alterations in the cancer microenvironment and capable of overcoming resistance to traditional therapies is necessary to improve cancer survival outcomes. These new therapeutic modalities should exhibit improved solubility, penetration capacity and bioavailability in the tumor microenvironment as well as enhanced target specificity compared to old generation compounds. The success of this endeavour will contribute to the advent of precision medicine leading to personalized therapeutic approaches for patients.

Background: Natural nanostructure materials have been involved in antitumor drug delivery systems due to their biocompatibility, biodegradation, and bioactive properties. Methods: These materials have contributed to advanced drug delivery systems in the roles of both bioactive compounds and delivery nanocarriers. Fucoidan, a valuable ocean material used in drug delivery systems, has been exploited in research on cancer and a variety of other diseases. Results: Although the uniqueness, structure, properties, and health benefits of fucoidan have been mentioned in various prominent reviews, current developments and designs of fucoidan-based formulations still need to be assessed to further develop an effective anticancer therapy. In this review, current important formulations using fucoidan as a functional material and as an anticancer agent will be discussed. This article will also provide a brief principle of the methods that incorporate functional nanostructure materials in formulations exploiting fucoidan. Conclusion: Current research and future perspectives on the use of fucoidan in anticancer therapy will advance innovative and important products for clinical uses.

Background: The potential of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) as theranostic agents for cancer has been investigated extensively. SPIONS can be utilized for diagnostic imaging, drug delivery as well as for therapeutic applications. SPIONS are of particular interest because of their potential for non-invasive diagnosis and non-invasive therapeutic applications. This article is a review of in vivo and clinical studies of SPIONs for diagnosis and treatment of breast, ovarian and cervical cancer. The current limitations of this technology with relation to clinical therapeutic applications and the potential to overcome these limitations are also discussed. Methods: NCBI Pubmed was searched for relevant documents by using keyword and MESH based search. The following keyword combinations were used: ‘breast cancer’ and SPION, ‘ovarian cancer’ and SPION, and ‘cervical cancer’ and SPION. The resulting list was manually scanned for the studies involving clinical and in vivo studies. Results: The 29 most relevant publications were identified and reviewed. Conclusion: Although numerous in vitro and in vivo studies have demonstrated the safety and effectiveness of the use of SPIONs for both diagnostic and therapeutic applications, there is relatively little progress towards translation to clinical applications involving breast, ovarian and cervical cancer.

Background: Typhonium is the largest genus in the Araceae family (~70 species), distributed in South Asia, Southeast Asia and Australia. Typhonium is well-known for its ethnopharmacological uses, and Southeast Asians consider it as an alternative medicine to treat cancer. This review elucidated the confirmed chemical structures of the isolated compounds of Typhonium and emphasized on their anticancer activities against various human cancer cells. Methods: Among several species, Typhonium blumei, T. flagelliforme, T. divaricatum and T. giganteum were extensively studied due to the presence of a class of secondary metabolites. All the available reports on Typhonium were included and discussed in this article. Results: Until now several groups of compounds, namely amino acids (1, 2), cinnamic acid (3), fatty acids (4-14), glycerol derivatives (15-18) and cerebrosides (19-34), flavonoids (35), hydantoins (36-38), lignin monomers (39-44), nucleobases (45-48), pheophorbides (49-52), phthalate (53), terpene and steroids (54-59) and vitamins (60, 61) were isolated and characterized from Typhonium. These phytochemicals were investigated for their anticancer properties, and results confirmed the promising growth inhibitory effect and anticancer activities against human lung, breast, prostate and colon cancer cells. The anticancer activity of these compounds appears to be mediated through the induction of apoptotic cell death. These phytochemicals further reported to exhibit other pharmacological efficacies, including anti-inflammatory, antioxidant, antiviral, anti-allergic, neuroprotective and hepato-protective properties. Conclusion: This is the first review to summarize the anticancer properties of all isolated compounds of Typhonium genus with confirmed chemical structures. Further advanced studies are necessary to establish the detailed signaling pathways that are involved in the anticancer property of the compounds.

Background: The introduction of Monoclonal Antibodies (mAbs) and small-molecule Tyrosine Kinase Inhibitors (TKIs) that target the Epidermal Growth Factor Receptor (EGFR), marks a huge step forward in the Pancreatic Cancer (PC) therapy. However, anti-EGFR therapy is found to be successful only in a fraction of patients. Although anti-EGFR agents have shown considerable clinical promise, a serious adverse event associated with anti- EGFR therapy has been challenging. At this juncture, there is still more to be done in the search for effective predictive markers with therapeutic applicability. Methods: A focused literature search was conducted to summarize the existing evidence on anti-EGFR agents in pancreatic cancer therapy. Results: This review discusses various anti-EGFR agents currently in use for PC therapy and potential adverse effects associated with it. Existing evidence on EGFR TKIs demonstrated better tolerant effects and outcomes with multiple toxic regimens. Anti-EGFR therapy in combination with chemotherapy is necessary to achieve the best clinical outcomes. Conclusion: Future prospective studies on the identification of additional biological agents and novel anti-EGFR agents are warranted.

Background: Cancer and other disorders such as inflammation, autoimmune diseases and diabetes are the major health problems observed all over the world. Therefore, identifying a therapeutic target molecule for the treatment of these diseases is urgently needed to benefit public health. C-Phycocyanin (C-PC) is an important light yielding pigment intermittently systematized in the cyanobacterial species along with other algal species. It has numerous applications in the field of biotechnology and drug industry and also possesses antioxidant, anticancer, antiinflammatory, enhanced immune function, including liver and kidney protection properties. The molecular mechanism of action of C-PC for its anticancer activity could be the blockage of cell cycle progression, inducing apoptosis and autophagy in cancer cells. Objectives: The current review summarizes an update on therapeutic applications of C-PC, its mechanism of action and mainly focuses on the recent development in the field of C-PC as a drug that exhibits beneficial effects against various human diseases including cancer and inflammation. Conclusion: The data from various studies suggest the therapeutic applications of C-PC such as anti-cancer activity, anti-inflammation, anti-angiogenic activity and healing capacity of certain autoimmune disorders. Mechanism of action of C-PC for its anticancer activity is the blockage of cell cycle progression, inducing apoptosis and autophagy in cancer cells. The future perspective of C-PC is to identify and define the molecular mechanism of its anti-cancer, anti-inflammatory and antioxidant activities, which would shed light on our knowledge on therapeutic applications of C-PC and may contribute significant benefits to global public health.

Background: Colorectal cancer is the third important cause of cancer-associated deaths across the world. Hence, there is an urgent need for understanding the complete mechanism associated with colorectal cancer, which in turn can be utilized toward early detection as well as the treatment of colorectal cancer in humans. Though colorectal cancer is a complex process and chemotherapy is the first step toward the treatment of colorectal cancer, recently several studies suggested that dietary phytochemicals may also aid significantly in reducing colorectal cancer risk in human. However, only few phytochemicals, specifically curcumin derived from the rhizomes of Curcuma longa, have better chemotherapeutic property, which might be because of its ability to regulate the activity of key factors associated with the initiation, promotion, as well as progression of tumors. Objectives: In the present review, the authors made an attempt to summarize the physiochemical properties of curcumin, which in turn prevent colorectal cancer via regulating numerous cell signaling as well as genetic pathways. Conclusion: Accumulated evidence suggested that curcumin suppresses tumour/colon cancer in various ways, (a) restricting cell cycle progression, or stimulating apoptosis, (b) restricting angiogenesis, anti-apoptotic proteins expression, cell survival signaling pathways & their cross-communication and (c) regulating immune responses. The information discussed in the present review will be useful in the drug discovery process as well as the treatment and prevention of colorectal cancer in humans.

Background: The curcumin-C3 (cur-C3) complex obtained from Curcuma longa rhizome is a combination of three curcuminoids, namely, curcumin, dimethoxycurcumin, and bisdemethoxycurcumin. Cur and curcuminoids have been extensively researched for their wide range of therapeutic properties against inflammatory diseases, diabetes, and cancer. Objective: In spite of their extensive medicinal properties, cur and curcuminoids have poor solubility and bioavailability due to their hydrophobicity. This limitation can be overcome by complexing cur-C3 with natural cyclic oligosaccharides, such as Cyclodextrin (CD). Methods: In this study, cur-C3 and CD (α, β) inclusion complexes (ICs) were prepared with different molar ratios and characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy, X-ray diffraction, and transmission electron microscopy. Results: The cur-C3 cyclodextrin ICs showed an increased entrapment efficiency of 97.8% and improved antioxidant activity compared to cur and can be used as an antioxidant to reduce cancer-related oxidative stress. Additionally, α- CD ICs of curcumin-C3 caused an increase in growth inhibition of Staphylococcus aureus. Conclusion: Our findings suggest that both α- and β-CDs are suitable carriers for cur-C3 and can be used as an effective treatment for cancer-associated oxidative stress and as a preventive treatment for nosocomial infections and pneumonia.