Cannabidiol Combination Enhances Photodynamic Therapy Effects on MCF-7 Breast Cancer Cells.

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 µg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.

Conjugation of Hypericin to Gold Nanoparticles for Enhancement of Photodynamic Therapy in MCF-7 Breast Cancer Cells.

Breast cancer, among the different types of cancer, is one of the most diagnosed cancers and the leading cause of mortalities amongst women. Factors, including genetic and epigenetic alterations in tumors, make it resistant to therapies, which results in treatment failures and/or recurrence. Furthermore, the existing therapies have many unfavorable side effects leading to poor prognosis and reduced therapeutic outcomes. Photodynamic therapy (PDT) is one of the most effective cancer therapies with increased selectivity and specificity toward cancer cells. As a result, the use of gold nanoparticles (AuNP) further improves the effectiveness of PDT by increasing the drug loading capacity into the cells. In this study, hypericin (Hyp) photosensitizer (PS) was adsorbed on gold nanoparticles (AuNPs) by sonication to achieve physical adsorption of the PS to AuNP. The resulting compound was characterized by FTIR, Zeta potential, UV-Vis spectroscopy, and TEM. The compound was used for the PDT treatment of MCF-7 human breast cancer in vitro. Cellular responses at 12 h post-PDT at 10 J/cm2 were observed. Cellular morphology, LDH membrane integrity, ATP luminescence assay, and Annexin V/PI staining were performed. The results demonstrated typical cell death morphological features while the biochemical responses indicated increased LDH and decreased ATP levels. In conclusion, this study presents an insight into the application of advanced PDT in breast cancer cells by inducing cancer cell death in vitro via apoptosis.

Photodynamic Therapy Induced Cell Death Mechanisms in Breast Cancer.

Breast cancer is the second most common cancer globally and the pioneering cause of mortality among women. It usually begins from the ducts or lobules, referred to as ductal carcinoma in situ, or lobular carcinoma in situ. Age, mutations in Breast Cancer Gene 1 or 2 (BRCA1 or BRCA2) genes, and dense breast tissue are the highest risk factors. Current treatments are associated with various side effects, relapse, and a low quality of life. Although conventional treatments, such as surgery and chemotherapy, have been used for decades, their adverse side effects on normal cells and tissues pose a major weakness, which calls for a non-invasive treatment option. Photodynamic therapy (PDT) has proven to be a promising form of cancer therapy. It is less invasive, target-specific, and with reduced cytotoxicity to normal cells and tissues. It involves the use of a photosensitizer (PS) and light at a specific wavelength to produce reactive oxygen species. One of the reasons for the target specificity is associated with the dense vascularization of cancer tissues, which tends to increase the surface area for the PS uptake. Photosensitizers are light-sensitive molecules, which result in cancer cell destruction followed by light irradiation. Depending on the localization of the PS within the cancer cell, its destruction may be via apoptosis, necrosis, or autophagy. This review focuses on the breast cancer etiopathology and PDT-induced cell death mechanisms in breast cancer cells.

Photobiomodulation at 660 nm Stimulates Fibroblast Differentiation.

BACKGROUND AND OBJECTIVES: Among many of the different complications that diabetic patients suffer, foot ulcers are the most challenging, and in many cases result in non-traumatic lower limb amputation and permanent disability. To alleviate this burden, new interventions such as photobiomodulation (PBM) have been utilized. However, the cellular pathways affected by PBM have not yet been fully recognized. The differentiation of fibroblasts into myofibroblasts forms a vital part of wound healing and is often impaired under diabetic conditions. Therefore, this study sought to investigate the effects of PBM at 660 nm on the transforming growth factor-ß1 (TGF-ß1)/Smad pathway and the differentiation of fibroblasts into myofibroblasts. STUDY DESIGN/MATERIALS AND METHODS: WS1 fibroblasts were treated with PBM using a wavelength of 660 nm at a fluence of 5 J/cm2 in normal, normal wounded, diabetic, and diabetic wounded models. Post-irradiation cellular responses were observed at 24, 48, and 72 hours to ascertain morphological changes and cell viability, and the expression of fibroblast differentiation markers (Thy-1 or CD90, extra domain A fibronectin or EDA-FN and α-smooth muscle actin or α-SMA), TGF-ß1, phosphorylated (p)TGF-ß receptor 1 (R1), and p-Smad2/3. RESULTS: There was a significant increase in cell viability in all irradiated cell models, and no real significant changes in TGF-ß1, pTGF-ß1R1, and p-Smad2/3. As incubation time post-irradiation increased, Thy-1 (CD90) decreased, while EDA-FN and α-SMA increased in wounded models. CONCLUSIONS: PBM at 660 nm with 5 J/cm2 was successful in stimulating the differentiation of fibroblasts into myofibroblasts in diabetic wounded cells, which was independent of the TGF-ß1/Smad pathway. Fibroblast transition into myofibroblasts is vital to wound healing, failure of which results in impaired healing; PBM is able to foster such a transition. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Enhancing Breast Cancer Treatment Using a Combination of Cannabidiol and Gold Nanoparticles for Photodynamic Therapy.

Indisputably, cancer is a global crisis that requires immediate intervention. Despite the use of conventional treatments over the past decades, it is acceptable to admit that these are expensive, invasive, associated with many side effects and, therefore, a reduced quality of life. One of the most possible solutions to this could be the use of gold nanoparticle (AuNP) conjugated photodynamic therapy (PDT) in combination with cannabidiol (CBD), a Cannabis derivative from the Cannabis sativa. Since the use of Cannabis has always been associated with recreation and psychoactive qualities, the positive effects of Cannabis or its derivatives on cancer treatment have been misunderstood and hence misinterpreted. On the other hand, AuNP-PDT is the most favoured form of treatment for cancer, due to its augmented specificity and minimal risk of side effects compared to conventional treatments. However, its use requires the consideration of several physical, biologic, pharmacologic and immunological factors, which may hinder its effectiveness if not taken into consideration. In this review, the role of gold nanoparticle mediated PDT combined with CBD treatment on breast cancer cells will be deliberated.

Role of photobiomodulation on the activation of the Smad pathway via TGF-ß in wound healing.

Wound healing is an essential process in which the separated or destroyed tissue attempts to restore itself into its normal state. In some instances, healing is prolonged and remains stagnant in the inflammatory phase, and is referred to as a chronic wound. At a cellular and molecular level, many factors are required during the process of successful wound healing, such as cytokines, polypeptide growth factors and components of the extracellular matrix (ECM). Transforming growth factor-beta (TGF-ß) is considered as one of the essential growth factors in wound healing. Working through the Smad pathway, it is the main inducer of fibroblast differentiation which is essential for wound healing. Photobiomodulation (PBM) shows significant advantages in wound healing, and may stimulate cellular processes and tissue regeneration that results in an increase in growth factors and a decrease in inflammatory cytokines. Moreover, it leads to enhanced cell proliferation, migration, angiogenesis, and increased adenosine triphosphate (ATP) and cytochrome C oxidase (CCO) activity. In this review paper, we discuss the effects of PBM and its role on the activation of the TGF-ß/Smad pathway in the process of wound healing.