An Overview of Potential Natural Photosensitizers in Cancer Photodynamic Therapy.

Cancer is one of the main causes of death worldwide. There are several different types of cancer recognized thus far, which can be treated by different approaches including surgery, radiotherapy, chemotherapy or a combination thereof. However, these approaches have certain drawbacks and limitations. Photodynamic therapy (PDT) is regarded as an alternative noninvasive approach for cancer treatment based on the generation of toxic oxygen (known as reactive oxygen species (ROS)) at the treatment site. PDT requires photoactivation by a photosensitizer (PS) at a specific wavelength (λ) of light in the vicinity of molecular oxygen (singlet oxygen). The cell death mechanisms adopted in PDT upon PS photoactivation are necrosis, apoptosis and stimulation of the immune system. Over the past few decades, the use of natural compounds as a photoactive agent for the selective eradication of neoplastic lesions has attracted researchers' attention. Many reviews have focused on the PS cell death mode of action and photonanomedicine approaches for PDT, while limited attention has been paid to the photoactivation of phytocompounds. Photoactivation is ever-present in nature and also found in natural plant compounds. The availability of various laser light setups can play a vital role in the discovery of photoactive phytocompounds that can be used as a natural PS. Exploring phytocompounds for their photoactive properties could reveal novel natural compounds that can be used as a PS in future pharmaceutical research. In this review, we highlight the current research regarding several photoactive phytocompound classes (furanocoumarins, alkaloids, poly-acetylenes and thiophenes, curcumins, flavonoids, anthraquinones, and natural extracts) and their photoactive potential to encourage researchers to focus on studies of natural agents and their use as a potent PS to enhance the efficiency of PDT.

Association of fibrinogen and plasminogen activator inhibitor-1 with diabetes mellitus.

As the state of hyperfibrinogenemia in diabetes patients occurs due to hyperglycemia which also activates the coagulative cascade ultimately stimulating hepatic fibrinogen synthesis and thus increases clotting factors and PAI-1 levels in the blood. Therefore, in present study our aim is to correlate between type of diabetes and plasma fibrinogen level and plasminogen activator inhibitor-1. This cross sectional study was conducted at Baqai Medical University (BMU) with the collaboration of Baqai Institute of Diabetology and Endocrinology, Karachi. Data was collected from 161 subjects, out of which 51 were control and 55 were subjects in each type 1 diabetes, type 2 diabetes simultaneously. Anthropometric measurements included measurement of weight, height, BMI and blood pressure which were done for each participant. Blood sugar levels and glycated hemoglobin, lipid profile, PAI-1 and fibrinogen were measured in cases and controls. Out of 161 subjects, 80 (49.7%) were male and 81 (50.3%) were female with mean age of 37.75±1.25 years. Fibrinogen level was significantly decreased in healthy subjects as compared to type 1 and type 2 diabetes subjects P-value<0.0001, however no significant difference was observed in fibrinogen level of type 1 diabetes subjects and type 2 diabetes subjects. Plasminogen activator inhibitor-1 of type 2 diabetes subjects was significantly increased as compared to type 1 diabetes subjects (P-value<0.05) but not significantly different to healthy subjects (P-value>0.05). Since, fibrinogen and plasminogen activator inhibitor type 1 was increased in diabetes patients this predisposed them to increased risk of coronary artery disease, our study further supports the clinical observation that diabetes is a thrombophillic condition.

Antiproliferative, antioxidant and binding mechanism analysis of prodigiosin from newly isolated radio-resistant Streptomyces sp. strain WMA-LM31.

Streptomyces genus are filamentous Gram positive bacteria, of great intrest, producing biologically active compounds. Recent market and consumer curiosity in natural products have forced scientist and industry for the development of new products with therapeutic potential. This study focuses on evaluation of antioxidant and anticancerous properties of prodigiosin from radio-resistant Streptomyces sp. strain WMA-LM31. A molecular docking approach was adopted to understand theoretical binding mechanism and affinity for anticancer targets. A radio-resistant bacterium, labelled as strain WMA-LM31, was isolated from desert soil and screened for its radio-resistant potential and prodigiosin production. 16S rRNA gene sequencing showed that the bacterium clusters to genus Streptomyces and found resistant to ultraviolet radiation (dosage of 2 × 103 J/m2). Strain WMA-LM31 produced a red color pigment in tryptone glucose yeast (TGY) medium.The LC-MS analysis of the purified compound showed a molar mass of 324 [m/z]+ matched the chemical formula C20H25N3O, identified as prodigiosin. The compound showed strong antioxidant (62.51%) activities along with significant inhibitory action against oxidative damages to bovine serum albumin (BSA) and mice liver lipids in comparison to standard ascorbic acid. IC50 values of HepG2 and HeLa cell lines was found at 12.66 and 14.83 µg/mL of prodigiosin concentration, respectively. Furthermore, molecular docking was performed with two different cancers macromolecular targets: [2O2F (Bcl-2) and 1DI8 (CDK-2)], and BSA (PDB id: 3V03). The results indicated that the binding affinity of prodigiosin to its target molecules is due to the presence of terminal pyrrole rings. It is concluded from the results that prodigiosin from Streptomyces sp. strain WMA-LM31 has strong antioxidant, anticancer and apoptotic properties. The knowledge of binding mechanisms and interactions of prodigiosin could provide future directions in designing potent target specifc drugs.