Green nanotech paradigm for enhancing sesquiterpene lactone therapeutics in cancer.

In the field of cancer therapy, sesquiterpene lactones (SLs) derived from diverse Dicoma species demonstrate noteworthy bioactivity. However, the translation of their full therapeutic potential into clinical applications encounters significant challenges, primarily related to solubility, bioavailability, and precise drug targeting. Despite these obstacles, our comprehensive review introduces an innovative paradigm shift that integrates the inherent therapeutic properties of SLs with the principles of green nanotechnology. To overcome issues of solubility, bioavailability, and targeted drug delivery, eco-friendly strategies are proposed for synthesizing nanocarriers. Green nanotechnology has emerged as a focal point in addressing environmental and health concerns linked to conventional treatments. This progressive approach of green nanotechnology holds promise for the development of safe and sustainable nanomaterials, particularly in the field of drug delivery. This groundbreaking methodology signifies a pioneering advancement in the creation of novel and effective anticancer therapeutics. It holds substantial potential for transforming cancer treatment and advancing the landscape of natural product research.

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.

Nano-phototherapy: Favorable prospects for cancer treatment.

Nanotechnology-based phototherapies have drawn interest in the fight against cancer because of its noninvasiveness, high flexibility, and precision in terms of cancer targeting and drug delivery based on its surface properties and size. Phototherapy has made remarkable development in recent decades. Approaches to phototherapy, which utilize nanomaterials or nanotechnology have emerged to contribute to advances around nanotechnologies in medicine, particularly for cancers. A brief overviews of the development of photodynamic therapy as well as its mechanism in cancer treatment is provided. We emphasize the design of novel nanoparticles utilized in photodynamic therapy while summarizing the representative progress during the recent years. Finally, to forecast important future research in this area, we examine the viability and promise of photodynamic therapy systems based on nanoparticles in clinical anticancer treatment applications and briefly make mention of the elimination of all reactive metabolites pertaining to nano formulations inside living organisms providing insight into clinical mechanistic processes. Future developments and therapeutic prospects for photodynamic treatments are anticipated. Our viewpoints might encourage scientists to create more potent phototherapy-based cancer therapeutic modalities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Ethnomedicinal Uses, Phytochemistry, and Anticancer Potentials of African Medicinal Fruits: A Comprehensive Review.

Africa is home to diverse medicinal plants that have been used for generations for the treatment of several different cancers and, presently, they are gaining interest from researchers as promising approaches to cancer treatment. This review aims to provide a comprehensive review of dietary and medicinal African fruits including their traditional uses, botanical description, ethnobotanical uses, bioactive phytochemical compositions, and anticancer properties investigated to date in vitro, in vivo, and in clinical studies. Data on recent updates concerning the traditional uses and anticancer properties of these fruits were collected from a myriad of available publications in electronic databases, such as Web of Science, PubMed, ScienceDirect, Scopus, SpringerLink, and Google Scholar. The results suggest that approximately 12 native or commercially grown African fruits belonging to different plant species, including Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia Africana, Annona muricata, Persea americana, and Punica granatum, have been reported for their potential as treatment options for the management of cancer. We further found that approximately eight different fruits from native plant species from Africa, namely, Sclerocarya birrea, Dovyalis caffra, Parinari curatellifolia, Mimusops caffra, Carpobrotus edulis, Vangueria infausta, Harpephyllum caffrum, and Carissa macrocarpa, have been widely used for the traditional treatment of different ailments but somehow failed to gain the interest of researchers for their use in anticancer research. In this review, we show the potential use of various fruits as anticancer agents, such as Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia Africana, Annona muricata, Persea americana, and Punica granatum; unfortunately, not enough reported research data have been published to gain thorough mechanistic insights and clinical applications. Additionally, we discuss the possibility of the utilization of potential phytochemicals from fruits like Persea americana and Punica granatum in anticancer research, as well as future directions.

Efficacy of Green Synthesized Nanoparticles in Photodynamic Therapy: A Therapeutic Approach.

Cancer is a complex and diverse disease characterized by the uncontrolled growth of abnormal cells in the body. It poses a significant global public health challenge and remains a leading cause of death. The rise in cancer cases and deaths is a significant worry, emphasizing the immediate need for increased awareness, prevention, and treatment measures. Photodynamic therapy (PDT) has emerged as a potential treatment for various types of cancer, including skin, lung, bladder, and oesophageal cancer. A key advantage of PDT is its ability to selectively target cancer cells while sparing normal cells. This is achieved by preferentially accumulating photosensitizing agents (PS) in cancer cells and precisely directing light activation to the tumour site. Consequently, PDT reduces the risk of harming surrounding healthy cells, which is a common drawback of conventional therapies such as chemotherapy and radiation therapy. The use of medicinal plants for therapeutic purposes has a long history dating back thousands of years and continues to be an integral part of healthcare in many cultures worldwide. Plant extracts and phytochemicals have demonstrated the ability to enhance the effectiveness of PDT by increasing the production of reactive oxygen species (ROS) and promoting apoptosis (cell death) in cancer cells. This natural approach capitalizes on the eco-friendly nature of plant-based photoactive compounds, offering valuable insights for future research. Nanotechnology has also played a pivotal role in medical advancements, particularly in the development of targeted drug delivery systems. Therefore, this review explores the potential of utilizing photosensitizing phytochemicals derived from medicinal plants as a viable source for PDT in the treatment of cancer. The integration of green photodynamic therapy with plant-based compounds holds promise for novel treatment alternatives for various chronic illnesses. By harnessing the scientific potential of plant-based compounds for PDT, we can pave the way for innovative and sustainable treatment strategies.

Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management.

Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to the need to continually screen natural products for effective and alternative anticancer bioactive principles. Alkaloids are chemical molecules that, due to their structural diversity, constitute a reserve for the discovery of lead compounds with interesting pharmacological activities. Several in vitro studies and a few in vivo findings have documented various cytotoxic and antiproliferative properties of alkaloids. This review describes chaetocochin J, neopapillarine, coclaurine, reflexin A, 3,10-dibromofascaplysin and neferine, which belong to different alkaloid classes with antineoplastic properties and have been identified recently from plants. Despite their low solubility and bioavailability, plant-derived alkaloids have viable prospects as sources of viable lead antitumor agents. This potential can be achieved if more research on these chemical compounds is directed toward investigating ways of improving their delivery in an active form close to target cells, preferably with no effect on neighboring normal tissues.

Cytotoxic Effects of Combinative ZnPcS4 Photosensitizer Photodynamic Therapy (PDT) and Cannabidiol (CBD) on a Cervical Cancer Cell Line.

The most prevalent type of gynecological malignancy globally is cervical cancer (CC). Complicated by tumor resistance and metastasis, it remains the leading cause of cancer deaths in women in South Africa. Early CC is managed by hysterectomy, chemotherapy, radiation, and more recently, immunotherapy. Although these treatments provide clinical benefits, many patients experience adverse effects and secondary CC spread. To minimize this, novel and innovative treatment methods need to be investigated. Photodynamic therapy (PDT) is an advantageous treatment modality that is non-invasive, with limited side effects. The Cannabis sativa L. plant isolate, cannabidiol (CBD), has anti-cancer effects, which inhibit tumor growth and spread. This study investigated the cytotoxic combinative effect of PDT and CBD on CC HeLa cells. The effects were assessed by exposing in vitro HeLa CC-cultured cells to varying doses of ZnPcS4 photosensitizer (PS) PDT and CBD, with a fluency of 10 J/cm2 and 673 nm irradiation. HeLa CC cells, which received the predetermined lowest dose concentrations (ICD50) of 0.125 µM ZnPcS4 PS plus 0.5 µM CBD to yield 50% cytotoxicity post-laser irradiation, reported highly significant and advantageous forms of cell death. Flow cytometry cell death pathway quantitative analysis showed that only 13% of HeLa cells were found to be viable, 7% were in early apoptosis and 64% were in late favorable forms of apoptotic cell death, with a minor 16% of necrosis post-PDT. Findings suggest that this combined treatment approach can possibly induce primary cellular destruction, as well as limit CC metastatic spread, and so warrants further investigation.

Curcumin a Natural Phenol and Its Therapeutic Role in Cancer and Photodynamic Therapy: A Review.

Cancer continues to cause an alarming number of deaths globally, and its burden on the health system is significant. Though different conventional therapeutic procedures are exploited for cancer treatment, the prevalence and death rates remain elevated. These, therefore, insinuate that novel and more efficient treatment procedures are needed for cancer. Curcumin, a bioactive, natural, phenolic compound isolated from the rhizome of the herbaceous plant turmeric, is receiving great interest for its exciting and broad pharmacological properties. Curcumin presents anticancer therapeutic capacities and can be utilized as a photosensitizing drug in cancer photodynamic therapy (PDT). Nonetheless, curcumin's poor bioavailability and related pharmacokinetics limit its clinical utility in cancer treatment. This review looks at the physical and chemical properties, bioavailability, and safety of curcumin, while focusing on curcumin as an agent in cancer therapy and as a photosensitizer in cancer PDT. The possible mechanisms and cellular targets of curcumin in cancer therapy and PDT are highlighted. Furthermore, recent improvements in curcumin's bioavailability in cancer therapy using nanoformulations and delivery systems are presented.

Synergistic effect of polymer functionalized graphene oxide system for breast cancer treatment.

The multifaceted drug carrier system is an emerging trend in delivering chemotherapeutic drugs and photosensitizers for the synergistic effect. In this work, we have designed a functionalized graphene oxide (GO) based carrier system for combined chemo-photodynamic therapeutic effects. Doxorubicin (DOX) and rose bengal (RB) were entrapped on the surface of GO via hydrophobic and π-π stacking interactions. The functional group determination, crystalline properties, surface morphology, and hydrodynamic size were evaluated using FT-IR, XRD, SEM, TEM, AFM, and DLS analysis. At 24 h, the entrapment efficiency was 65 % DOX and 40.92 % RB, and the loading capacities were 16.9 % DOX and 5.68 % RB observed at 30 min. The drug release percentage was higher in pH-2.6 rather than in pH-5.5, 6.8, and 7.4 pH environments. The in-vitro toxicity analysis using the LDH assay reveals that the DOX and RB co-loaded carriers had a significant cytotoxic effect on MCF-7 cells, indicating that the carrier could improve the therapeutic efficacy of DOX. Morphological changes were studied using inverted light microscopy; the cells were irradiated with a laser 525 nm 10 J/cm2 for 2 min 51 sec, and it was observed that the DOX and RB co-loaded carrier with laser-irradiated cells exposed the high-level morphological changes with the occurrence of apoptotic cell death. Compared to free DOX, the DOX/RB co-loaded carrier + laser had an efficient anticancer activity, as confirmed by DAPI staining cell uptake, flow cytometry, and intracellular ROS generation analysis. The DOX and RB co-loaded carrier clearly exhibits the RB-mediated photodynamic action on MCF-7 cells in response to external laser light irradiation. It permits an on-demand dual-payload release to trigger an instantaneous photodynamic and chemo treatment for cancer cell eradication. Finally, the ensuing dual-agent release is probable to successfully fight cancer via a synergistic effect.

The In-Vitro Effect of Homeopathically Prepared Rubus idaeus and 680 nm Laser Irradiation on Cervical Cancer Cells.

BACKGROUND: Cervical cancer (CC) is the second leading cancer in women and is the most common in those aged 15 to 44 years. Medicinal plant extracts have been used as homeopathic preparations for health benefits. Rubus idaeus (RI) is used to treat disorders of the female genital tract and produces cytotoxic effects. However, the use of homeopathically prepared RI in combination with low level laser therapy has not previously been explored. AIM: The study aims to investigate the in-vitro effects of homeopathically prepared RI alone and in combination as a potential photosensitizer with Low-level laser irradiation (LLLI) at fluencies of 5, 10, and 15 J/cm2. METHODS: HeLa CC cells were treated with RI (D3, D6, and 30cH homeopathic preparations). Cells were then treated with RI IC50 and 680 nm laser diode at 5, 10, and 15 J/cm2 fluencies, and the results compared with untreated control cells. Trypan blue viability, lactate dehydrogenase (LDH) cytotoxicity, and adenosine triphosphate (ATP) proliferation assays were used to analyze the cellular dose-responses along with inverted microscopy, Hoechst staining and Annexin-V/PI staining. RESULTS: RI D3 alone demonstrated an ability to reduce cellular viability to 59% and also to reduce ATP levels. The subsequent combined treatment protocol of RI D3 with all fluencies of laser demonstrated an increase in cellular ATP and increased LDH levels compared with the control. CONCLUSION: The increased ATP and LDH levels observed in the combined treatment protocol of 680 nm laser and RI D3 at fluencies of 5, 10 and 15 J/cm2, show that the Warburg effect might have been induced in the CC cells - an increase in glucose uptake and the preferential production of lactate, even in the presence of oxygen. More research, including work on other cell lines, needs to be conducted to identify if RI and perhaps a different wavelength of laser irradiation could have potential in inducing cell death in cancer cells.

The Therapeutic Efficacy of Punica granatum and Its Bioactive Constituents with Special Reference to Photodynamic Therapy.

Punica granatum (P. granatum) is a fruit-bearing tree from the Punicaceae family, indigenous to Iran. This plant has healing qualities that have drawn the interest of the medical community as an alternative treatment for malignancies and non-malignancies. Its healing quality is due to the phytochemicals present in the plant. These include ellagic acid, punicic acid, phenols, and flavonoids. In traditional medicine, P. granatum has been used in treating diseases such as dysentery, bleeding disorders, leprosy, and burns. This review explores the effects of the phytochemical constituents of P. granatum on photodynamic therapy for cancer, chronic inflammation, osteoarthritis, and viral infections. Its antioxidant and antitumor effects play a role in reduced free radical damage and cancer cell proliferation. It was concluded that P. granatum has been used for many disease conditions for a better therapeutic outcome. This paper will give visibility to more studies and expand the knowledge on the potential use of P. granatum in photodynamic cancer treatment.

Light-Activated Phytochemicals in Photodynamic Therapy for Cancer: A Mini Review.

Background: Cancer is a serious life-threatening disease often thought of as a deadly and painful disease with no permanent cure. With the advancement of medical science, there have been several clinically approved treatment options developed over the past decade. Photodynamic therapy (PDT) is one such approved minimally invasive light-based therapeutic option for many cancers. Selection of a suitable photosensitizer (PS) is an important step in PDT for improved therapeutic outcomes. Efforts to discover more efficient PSs continue for optimal PDT. Objective: This review discusses the available natural PS of plant origin, the role of phytochemicals in the application of PDT of cancer, specific localization of PS in various cell organelles, and photochemical reactions. Materials and methods: Owing to the substantial side effects, many biomedical research fields are currently focusing on natural compounds with chemotherapeutic potential with environmentally sustainable green approaches. Medicinal plant extracts have been used since ancient times for the treatment of various ailments. Plants are a natural source of many bioactive compounds with pharmaceutical potential and there have been some efforts made to discover potential new compounds from plants with photosensitizing properties for effective PDT outcomes. Results and conclusions: The PDT application in the current scenario raises some questions, such as most effective PS, its administration, the time of irradiation, light source, sensitivity of cells toward PS, and so forth. PDT effects can be direct or indirect. Owing to the direct effect of the PDT, most of the tumoral mass is destroyed. In the cancer cells that were not directly affected, secondary effects such as vascular effects, apoptosis induction, inflammation, and generation of an immune response may occur; however, the complex nature of PDT tissue response is not fully established.

Multi-Target Potential of Berberine as an Antineoplastic and Antimetastatic Agent: A Special Focus on Lung Cancer Treatment.

Despite therapeutic advancements, lung cancer remains the principal cause of cancer mortality in a global scenario. The increased incidence of tumor reoccurrence and progression and the highly metastatic nature of lung cancer are of great concern and hence require the investigation of novel therapies and/or medications. Naturally occurring compounds from plants serve as important resources for novel drugs for cancer therapy. Amongst these phytochemicals, Berberine, an alkaloid, has been extensively explored as a potential natural anticancer therapeutic agent. Several studies have shown the effectiveness of Berberine in inhibiting cancer growth and progression mediated via several different mechanisms, which include cell cycle arrest, inducing cell death by apoptosis and autophagy, inhibiting cell proliferation and invasion, as well as regulating the expression of microRNA, telomerase activity, and the tumor microenvironment, which usually varies for different cancer types. In this review, we aim to provide a better understanding of molecular insights of Berberine and its various derivative-induced antiproliferative and antimetastatic effects against lung cancer. In conclusion, the Berberine imparts its anticancer efficacy against lung cancers via modulation of several signaling pathways involved in cancer cell viability and proliferation, as well as migration, invasion, and metastasis.

Rubus Capped Zinc Oxide Nanoparticles Induce Apoptosis in MCF-7 Breast Cancer Cells.

Rubus fairholmianus (RF) has widely been used to treat various ailments, including pain, diabetes, and cancer. Zinc oxide nanoparticles (ZnO NPs) have drawn attention in modern healthcare applications. Hence, we designed this study to synthesize zinc oxide (ZnO) nanoparticles using R. fairholmianus root extract to investigate its synergistic cytotoxic effect on MCF-7 cells and explore the possible cell death mechanism. ZnO NPs were synthesized via green synthesis using R. fairholmianus root extract, and the effect on MCF-7 cells was determined by looking at cellular morphology, proliferation, cytotoxicity, apoptosis, and reactive oxygen species (ROS). The results showed that cellular proliferation was reduced following treatment with R. fairholmianus capped zinc oxide nanoparticles (RFZnO NPs), while cytotoxicity and ROS were increased. There was also an increase in apoptosis as indicated by the significant increase in cytoplasmic cytochrome c and caspase 3/7 (markers of apoptosis), as well as increased levels of pro-apoptotic proteins (p53, Bax) and decreased levels of anti-apoptotic protein (Bcl-2). In conclusion, these results showed that RFZnO NPs induce apoptosis in breast cancer cells via a mitochondria-mediated caspase-dependent apoptotic pathway and suggest the use of acetone root extract of R. fairholmianus for the treatment of cancer-related ailments.

The effect of photomodulation on fibroblast growth factor and the Ras/MAPK signalling pathway: a review.

OBJECTIVE: Current therapies and technologies used to treat hard-to-heal diabetic wounds are limited to a 50% healing rate. The rise in the percentage of lower limb non-traumatic amputations in patients with diabetes has caused an increased demand for alternative, effective and safe treatment modalities. Photobiomodulation therapy (PBMT) utilises light to induce physiological changes and provide therapeutic benefits and has been shown to increase the healing of hard-to-heal wounds through the release of growth factors. The aim of this narrative review is to investigate the effect of photobiomodulation (PBM) on fibroblast growth factor (FGF) and the role of the Ras/MAPK signalling pathway in diabetic wound healing. METHOD: Relevant journal articles were obtained through PubMed and Google Scholar. RESULTS: Experimental and clinical findings from the review show that PBM can stimulate the release of growth factors, including FGF, an essential cytokine in wound healing, and one which is present at lower concentrations in diabetic wounds. There is also activation of the Ras/MAPK signalling pathway. CONCLUSION: One mechanism through which healing may be stimulated by PBM is via the FGF-Ras/MAPK signalling pathway, although strong evidence under hyperglycaemic conditions is lacking.

In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells.

Globally, lung cancer has remained the leading cause of morbidity and mortality in men and women. To enhance photodynamic therapeutic effects in vitro, the present study was designed to reduce dose-dependence in photodynamic therapy (PDT) and evaluate the anticancer effects of Dicoma anomala (D. anomala) root extracts (i.e., chloroform (Chl), ethyl acetate (EtOAc), and methanol (MeOH)) on A549 lung cancer cells. The most active extract of D. anomala (D.A) was used to establish the 50% inhibitory concentration (IC50), which was further used to evaluate the anticancer efficacy of D.A in combination with ZnPcS4-mediated PDT IC50. The study further evaluated cell death mechanisms by cell viability/ cytotoxicity (LIVE/DEADTM assay), flow cytometry (Annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) staining), immunofluorescence (p38, p53, Bax, and caspase 3 expressions), and fluorometric multiplex assay (caspase 8 and 9) 24 h post-treatment with IC50 concentrations of ZnPcS4-mediated PDT and D.A MeOH root extract. Morphological changes were accompanied by a dose-dependent increase in cytotoxicity, decrease in viability, and proliferation in all experimental models. Apoptosis is the highly favored cell death mechanism observed in combination therapy groups. Apoptotic activities were supported by an increase in the number of dead cells in the LIVE/DEADTM assay, and the upregulation of p38, p53, Bax, caspase 3, 8, and 9 apoptotic proteins. In vitro experiments confirmed the cytotoxic and antiproliferative effects of D.A root extracts in monotherapy and in combination with ZnPcS4-mediated PDT. Taken together, our findings demonstrated that D.A could be a promising therapeutic candidate worth exploring in different types of cancer.

Photodynamic Effects of Thuja occidentalis on Lung Cancer Cells.

The global incidence and mortality rates resulting from lung cancer encapsulate a need to identify more effective treatment protocols. Photodynamic therapy (PDT) and homeopathy offer possible anticancer therapies as part of a multi-disciplinary approach. Studies have identified the anticancer effects of Thuja occidentalis L. plant extracts. The aim of this study was to investigate the effects of Thuja occidentalis (TO) homeopathic mother tincture and TO mediated PDT (TO-PDT) on A549 lung cancer cells. Commercially available A549 cells were pre-treated with TO, or laser irradiation at 660 nm, or the combined treatment (TO-PDT). Cells were analyzed morphologically by inverted light microscopy and Hoechst stain; and biochemically by lactate dehydrogenase (LDH), adenosine triphosphate (ATP), and trypan blue assays. Cells treated with TO and TO-PDT demonstrated morphological changes in the cell and cell nuclei indicative of cell death. These groups exhibited a dose dependent increase in LDH release and a decrease in ATP levels and cell viability indicating its cytotoxic and antiproliferative potential. Furthermore, at the same doses, TO when photoactivated in PDT induced enhanced anticancer responses thereby surpassing the effects of treatment with the tincture alone. Results demonstrate how the direct cytotoxic effects of TO can be improved when administered as a photosensitizer in PDT to promote cancer cell death.

Photoactive Herbal Compounds: A Green Approach to Photodynamic Therapy.

Photodynamic therapy (PDT) is a minimally invasive, alternative, and promising treatment for various diseases, including cancer, actinic keratosis, Bowen's disease, macular degeneration, and atherosclerotic plaques. PDT involves three different components, photosensitizers (PS), molecular oxygen, and light. The photoactivation of administered PSs using a specific wavelength of light in the presence of molecular oxygen leads to the generation of reactive oxygen species that leads to tumour cell death. Photosensitizing potentials of many commercially available compounds have been reported earlier. However, the possibilities of PDT using herbal medicines, which contain many photosensitizing phytochemicals, are not much explored. Medicinal plants with complex phytochemical compound mixtures have the benefit over single compounds or molecules in the treatment of many diseases with the benefit of low or reduced toxic side effects. This review emphasizes the role of various herbal medicines either alone or in combination to enhance the therapeutic outcome of photodynamic therapy.

Enhancement of Conventional and Photodynamic Therapy for Treatment of Cervical Cancer with Cannabidiol.

Cervical cancer (CC) is the fourth most diagnosed cancer in women worldwide. Conventional treatments include surgery, chemo- and radiotherapy, however these are invasive and may cause severe side effects. Furthermore, approximately 70% of late-stage CC patients experience metastasis, due to treatment resistance and limitations. Thus, there is a dire need to investigate alternative therapeutic combination therapies. Photodynamic therapy (PDT) is an alternative CC treatment modality that has been clinically proven to treat primary CC, as well as to limit secondary metastasis. Since PDT is a non-invasive localized treatment, with fewer side effects and lessened resistance to dose repeats, it is considered far more advantageous. However, more clinical trials are required to refine its delivery and dosing, as well as improve its ability to activate specific immune responses to eradicate secondary CC spread. Cannabidiol (CBD) isolates have been shown to exert in vitro CC anticancer effects, causing apoptosis post treatment, as well as inducing specific immune responses, which obstruct tumor invasion and angiogenesis, and so hinder CC metastatic spread. This review paper discusses the current conventional and alternative PDT treatment modalities for CC, as well as their limitations over the last 10 years. It has a particular focus on the combinative administration of CBD with these treatments in order to prevent CC secondary migration and so possibly encourage future research studies to focus on this synergistic effect to eradicate CC.