Role of Bcl-2 Family Proteins in Photodynamic Therapy Mediated Cell Survival and Regulation.

Photodynamic therapy (PDT) is a treatment modality that involves three components: combination of a photosensitizer, light and molecular oxygen that leads to localized formation of reactive oxygen species (ROS). The ROS generated from this promising therapeutic modality can be lethal to the cell and leads to consequential destruction of tumor cells. However, sometimes the ROS trigger a stress response survival mechanism that helps the cells to cope with PDT-induced damage, resulting in resistance to the treatment. One preferred mechanism of cell death induced by PDT is apoptosis, and B-cell lymphoma 2 (Bcl-2) family proteins have been described as a major determinant of life or death decision of the death pathways. Apoptosis is a cellular self-destruction mechanism to remove old cells through the biological event of tissue homeostasis. The Bcl-2 family proteins act as a critical mediator of a life-death decision of cells in maintaining tissue homeostasis. There are several reports that show cancer cells developing resistance due to the increased interaction of the pro-survival Bcl-2 family proteins. However, the key mechanisms leading to apoptosis evasion and drug resistance have not been adequately understood. Therefore, it is critical to understand the mechanisms of PDT resistance, as well as the Bcl-2 family proteins, to give more insight into the treatment outcomes. In this review, we describe the role of Bcl-2 gene family proteins' interaction in response to disease progression and PDT-induced resistance mechanisms.

In vitro combined effect of Doxorubicin and sulfonated zinc Phthalocyanine-mediated photodynamic therapy on MCF-7 breast cancer cells.

Doxorubicin is a broad-spectrum antibiotic and anticancer drug used to treat a variety of human malignancies like breast cancer and leukaemia. Unfortunately, a dose-dependent side effect of this drug is common, representing a major obstacle to its use despite its therapeutic efficacy. Photodynamic therapy is an emerging non-invasive potential adjuvant for conventional cancer treatment. In an attempt to circumvent the dose-limiting effect of doxorubicin, this study aimed to investigate cellular anticancer activity of doxorubicin and sulfonated zinc phthalocyanine-mediated photodynamic therapy on MCF-7 cells alone and in combination. Furthermore, we investigated the cell death pathway resulting from the combination treatment. MCF-7 cells were incubated with 0.5 µM concentration of doxorubicin for 20 h, afterwards, various concentrations of sulfonated zinc phthalocyanine were added and incubated for 4 h. Cells were irradiated using a 681.5 nm diode laser at 4.53 mW/cm2 for 18 min 24 s (5 J/cm2). Cell viability and proliferation were measured using trypan blue assay and homogeneous adenosine triphosphate quantitation assay, respectively, while qualitative changes in cellular morphology were observed under inverted light microscopy. Cellular DNA damage was assessed under fluorescent microscopy and Annexin V/propidium iodide stain was used to investigate the cell death pathway. Findings from this study shown that combined treatment with doxorubicin and photodynamic therapy was more effective in inhibiting the proliferation and growth of MCF-7 cells. Overall, the results indicate that combination of smaller dose of doxorubicin with photodynamic therapy is a promising combined treatment strategy for breast carcinoma. However, this combination warrants further investigation.

A novel approach to low-temperature synthesis of cubic HfO2 nanostructures and their cytotoxicity.

The development of a strategy to stabilise the cubic phase of HfO2 at lower temperatures is necessary for the emergence of unique properties that are not realised in the thermodynamically stable monoclinic phase. A very high temperature (>2600 °C) is required to produce the cubic phase of HfO2, whereas the monoclinic phase is stable at low temperature. Here, a novel rapid synthesis strategy was designed to develop highly crystalline, pure cubic-phase HfO2 nanoparticles (size <10 nm) using microwave irradiation. Furthermore, the as-prepared nanoparticles were converted to different morphologies (spherical nanoparticles and nanoplates) without compromising the cubic phase by employing a post-hydrothermal treatment in the presence of surface modifiers. The cytotoxicities and proliferative profiles of the synthesised cubic HfO2 nanostructures were investigated over the MCF-7 breast cancer cell line, along with caspase-3/7 activities. The low-temperature phase stabilisation was significantly attributed to surface imperfections (defects and deformations) induced in the crystal lattice by the desirable presence of Na2S·xH2O and NaOH. Our work provides unprecedented insight into the stabilisation of nanoscale cubic-phase HfO2 in ambient environments; the method could be extended to other challenging phases of nanomaterials.

Phthalocyanine induced phototherapy coupled with Doxorubicin; a promising novel treatment for breast cancer.

INTRODUCTION: Globally, breast cancer is the most common life-threatening malignant disease among women. Adjuvant chemotherapeutic treatment of anthracycline-based chemotherapy (e.g., doxorubicin) has been shown to be more advantageous over non-anthracycline-based therapies, yet possess the tenacity of developing resistance and potential side effects which have limited its use in the clinical setting. These reasons necessitate combining doxorubicin with emerging photodynamic treatment regimens. Areas covered: In this review, the authors have concisely explained doxorubicin chemotherapy and the photobiological processes of phthalocyanine triggered photodynamic therapy (PDT). A literature search was conducted and reports demonstrating the use of doxorubicin and photodynamic therapy as a treatment modality for breast cancer were identified. More emphasis was made on studies demonstrating the efficacy and improved anticancer effect of combining chemotherapy with photodynamic therapy. However, it was concluded that for this combination therapy, still in it's infancy, it could be relevant when integrated into standard treatment. Expert Commentary: To these effects, comprehensive models based on experimental evaluations are needed for rational design of anthracycline-based chemotherapy and PDT to be integrated into the clinical setting.

Caspase dependent apoptotic inhibition of melanoma and lung cancer cells by tropical Rubus extracts.

Rubus fairholmianus Gard. inhibits human melanoma (A375) and lung cancer (A549) cell growth by the caspase dependent apoptotic pathway. Herbal products have a long history of clinical use and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. The plants and plant derived products became the basis of traditional medicine system throughout the world for thousands of years. The effects of R. fairholmianus root acetone extract (RFRA) on the proliferation of A375 and A549 cells was examined in this study. RFRA led to a decrease in cell viability, proliferation and an increase in cytotoxicity in a dose dependent manner when compared with control and normal skin fibroblast cells (WS1). The morphology of treated cells supported apoptotic cell death. Annexin V/propidium iodide staining indicated that RFRA induced apoptosis in A375 and A549 cells and the percentages of early and late apoptotic populations significantly increased. Moreover, the apoptotic inducing ability of RFRA when analysing effector caspase 3/7 activity, indicated a marked increase in treated cells. In summary, we have shown the anticancer effects of RFRA in A375 and A549 cancer cells via induction of caspase dependent apoptosis in vitro. The extract is more effective against melanoma; which may suggest the usefulness of RFRA-based anticancer therapies.

A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms.

This review article presents an extensive examination of risk factors for breast cancer, treatment strategies with special attention to photodynamic therapy and natural product based treatments. Breast cancer remains the most commonly occurring cancer in women worldwide and the detection, treatment, and prevention are prominent concerns in public health. Background information on current developments in treatment helps to update the approach towards risk assessment. Breast cancer risk is linked to many factors such as hereditary, reproductive and lifestyle factors. Minimally invasive Photodynamic therapy (PDT) can be used in the management of various cancers; it uses a light sensitive drug (a photosensitizer, PS) and a light of visible wavelength, to destroy targeted cancer cells. State of the art analyses has been carried out to investigate advancement in the search for the cure and control of cancer progression using natural products. Traditional medicinal plants have been used as lead compounds for drug discovery in modern medicine. Both PDT and plant derived drugs induce cell death via different mechanisms including apoptosis, necrosis, autophagy, cell cycle regulation and even the regulation of various cell signalling pathways.

Antitumor and Wound Healing Properties of Rubus ellipticus Smith.

The present investigation has been undertaken to study the antioxidant, antitumor, and wound healing properties of Rubus ellipticus. The R. ellipticus leaves were extracted using organic solvents in Soxhlet and were subjected to in vitro antioxidant assays. R. ellipticus leaf methanol (RELM) extract, which showed higher in vitro antioxidant activity, was taken for the evaluation of in vivo antioxidant, antitumor, and wound healing properties. Acute oral and dermal toxicity studies showed the safety of RELM up to a dose of 2 g/kg. A significant wound healing property was observed in incision, excision, and Staphylococcus aureus-induced infected wound models in the treatment groups compared to the control group. A complete epithelialization period was noticed during the 13(th) day and the 19(th) day. A 250-mg/kg treatment was found to prolong the life span of mice with Ehrlich ascite carcinoma (EAC; 46.76%) and to reduce the volume of Dalton's lymphoma ascite (DLA) solid tumors (2.56 cm(3)). The present study suggests that R. ellipticus is a valuable natural antioxidant and that it is immensely effective for treating skin diseases, wounds, and tumors.

Antitumor and wound healing properties of Rubus niveus Thunb. root.

The main objective of this study is to highlight the importance of Rubus niveus in the pharmaceutical industry for the development of cost-effective drugs. The study was undertaken to explore the HPLC profile, wound healing, antitumor, and free radical scavenging properties of R. niveus. The root of R. niveus was extracted using organic solvents and subjected to in vitro antioxidant assays. Acetone extract, which showed better in vitro antioxidant properties, was evaluated for in vivo antioxidant, wound healing, and antitumor properties. The polyphenolic acetone extract showed significant in vivo antioxidant, wound healing, and antitumor properties. In the wound healing study, complete epithelialization was noticed during the 13th to 17th days for treated groups. The 250 mg/kg group was found to prolong the life span of mice with Ehrlich ascites carcinoma (70.04%) and reduced the volume of Daltons lymphoma ascites solid tumors (2.07 cm3). The HPLC analysis of acetone extract revealed the presence of Quercetin, a natural flavonoid with the retention time of 20.89 min. The results of the current study suggest the use of R. niveus as a valuable natural antioxidant that has an immense scope as an effective source to cure skin diseases, wounds, and tumors.