Background Anti-cancer therapy is more successful when it can also induce an immunogenic form of cancer cell death (ICD). Therefore, when developing new treatment strategies, it is extremely important to choose methods that induce ICD and thereby activate anti-tumor immune response leading to the most effective destruction of tumor cells. The aim of this work was to analyze whether the clinically widely used photosensitizers, photosens (PS) and photodithazine (PD), can induce ICD when used in photodynamic therapy (PDT). Methods Cell death in murine glioma GL261 or fibrosarcoma MCA205 cells was induced by PS- or PD-PDT and cell death was analyzed by MTT or flow cytometry. Intracellular distribution of PS and PD was studied by using the laser scanning microscope. Calreticulin exposure and HMGB1 and ATP release were detected by flow cytometry, ELISA and luminescence assay, respectively. Immunogenicity in vitro was analyzed by co-culturing of dying cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and maturation (CD11c⁺CD86⁺, CD11c⁺CD40⁺) of BMDCs and production of IL-6 in the supernatant were measured. In vivo immunogenicity was analyzed in mouse tumor prophylactic vaccination model. Results We determined the optimal concentrations of the photosensitizers and found that at a light dose of 20 J/cm² (λex 615–635 nm) both PS and PD efficiently induced cell death in glioma GL261 and fibrosarcoma MCA205 cells. We demonstrate that PS localized predominantly in the lysosomes and that the cell death induced by PS-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) and by ferrostatin-1 and DFO (ferroptosis inhibitors), but not by the necroptosis inhibitor necrostatin-1 s. By contrast, PD accumulated in the endoplasmic reticulum and Golgi apparatus, and the cell death induced by PD-PDT was inhibited only by z-VAD-fmk. Dying cancer cells induced by PS-PDT or PD-PDT emit calreticulin, HMGB1 and ATP and they were efficiently engulfed by BMDCs, which then matured, became activated and produced IL-6. Using dying cancer cells induced by PS-PDT or PD-PDT, we demonstrate the efficient vaccination potential of ICD in vivo. Conclusions Altogether, these results identify PS and PD as novel ICD inducers that could be effectively combined with PDT in cancer therapy.

Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy.

While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction of patients are refractory to ICIs employed as standalone therapeutics, necessitating the development of combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest as combinatorial partners for ICIs, at least in part owing to their ability to initiate a tumor-targeting adaptive immune response. However, compared with either approach alone, combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity. Here, we discuss accumulating evidence on the therapeutic interactions between ICD inducers and immunotherapy with ICIs in oncological settings, identify key factors that may explain discrepancies between preclinical and clinical findings, and propose strategies that address existing challenges to increase the efficacy of these combinations in patients with cancer.

It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET), polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties.

Cold atmospheric plasma (CAP) has shown its antitumor activity in both in vitro and in vivo systems. However, the mechanisms at the basis of CAP‐cell interaction are not yet completely understood. The aim of this study is to investigate CAP proapoptotic effect and identify some of the molecular mechanisms triggered by CAP in human T‐lymphoblastoid leukemia cells. CAP treatment was performed by means of a wand electrode DBD source driven by nanosecond high‐voltage pulses under different operating conditions. The biological endpoints were assessed through flow cytometry and real‐time PCR. CAP caused apoptosis in Jurkat cells mediated by p53 upregulation. To test the involvement of intrinsic and/or extrinsic pathway, the expression of Bax/Bcl‐2 and caspase‐8 was analyzed. The activation of caspase‐8 and the upregulation of Bax and Bcl‐2 were observed. Moreover, CAP treatment increased ROS intracellular level. The situation reverts after a longer time of treatment. This is probably due to compensatory cellular mechanisms such as the posttranscriptional upregulation of SOD1, CAT, and GSR2. According to ROS increase, CAP induced a significant increase in DNA damage at all treatment conditions. In conclusion, our results provide a deeper understanding of CAP potential in the oncological field and pose the basis for the evaluation of its toxicological profile.

Introduction: Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional supplements are increasingly sold. Conversely, safety concerns have been raised about the promutagens and procarcinogens alkenylbenzenes contained in OB. Areas covered: A critical review of the current status of OB as a nutraceutical, the pharmacology of its bioactive components, the rationale for its indications, and its safety. Expert opinion: Due to the polyphenolic and flavonoidic content, OB can be considered as an important ingredient in healthy diets; OB preparations may be effective as chemopreventive agents or adjunctive therapy in the treatment of different clinical conditions. From a toxicological perspective, since the tumorigenic potential of alkenylbenzenes is counteracted by other OB constituents such as nevadensin, it can be concluded that OB consumption in food and preparations is safe. The only concern relates to OB essential oils: in this case, a concentration limit for alkenylbenzenes should be precautionary defined, and the use of plant chemotypes with no or low levels of these alkylbenzenes for the preparation of essential oils should be made compulsory.