Luteolin is a flavonoid, which has been extensively investigated due to its antitumor effects; however, the underlying mechanisms of its action remain largely unknown. The present study aimed to investigate the role of luteolin in breast cancer (BC), and explored how luteolin suppresses the growth and induces the apoptosis of BC cells. The MTS assay was used to determine the anticancer activity of luteolin. Colony formation and Transwell assays were performed to evaluate the effects of luteolin on cell growth and invasion. Cell cycle progression and apoptosis were analyzed by flow cytometry. In addition, western blotting was performed to analyze cellular apoptosis and signaling pathways elicited by luteolin. The present study revealed that the proliferation of the BC cell line MDA‑MB‑231 was effectively suppressed by luteolin in a dose‑dependent manner. Additionally, luteolin was revealed to increase apoptotic rates in BC cells. Dose‑dependent cell cycle arrest in S phase was observed following treatment with luteolin in MDA‑MB‑231 cells. Mechanistically, luteolin reduced telomerase levels in a dose‑dependent manner. Additionally, luteolin inhibited phosphorylation of the nuclear factor‑κB inhibitor α and its target gene c‑Myc, to suppress human telomerase reverse transcriptase (hTERT) expression, which encodes the catalytic subunit of telomerase. Collectively, the results of the present study indicated that luteolin may inhibit BC cell growth by targeting hTERT, suggesting that the mechanism of hTERT regulation by luteolin may justify further study regarding its potential as a therapeutic target for BC treatment.
Cancer immunotherapy has received more and more attention from cancer researchers over the past few decades. Various methods such as cell therapy, immune checkpoint blockers, and cancer vaccines alone or in combination therapies have achieved relatively satisfactory results in cancer therapy. Among these immunotherapy-based methods, cancer vaccines alone have not yet had the necessary efficacy in the clinic. Therefore, nanomaterials have increased the efficacy and ef-fectiveness of cancer vaccines by increasing their half-life and durability, promoting tumor mi-croenvironment (TME) reprogramming, and enhancing their anti-tumor immunity with minimal toxicity. In this review, according to the latest studies, the structure and different types of nanovaccines, the mechanisms of these vaccines in cancer treatment, as well as the advantages and disadvantages of these nanovaccines are discussed.
Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.
1 January 2021 in Oxidative Medicine and Cellular Longevity
Purpose. Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse effects on the normal cells/tissues, especially cardiotoxicity. The use of resveratrol may mitigate the doxorubicin‐induced cardiotoxic effects. For this aim, we systematically reviewed the potential chemoprotective effects of resveratrol against the doxorubicin‐induced cardiotoxicity. Methods. In the current study, a systematic search was performed based on Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guideline for the identification of all relevant studies on “the role of resveratrol on doxorubicin‐induced cardiotoxicity” in the electronic databases of Web of Science, PubMed, and Scopus up to March 2021 using search terms in their titles and abstracts. Two hundred and eighteen articles were screened in accordance with a predefined set of inclusion and exclusion criteria. Finally, 33 eligible articles were included in this systematic review. Results. The in vitro and in vivo findings demonstrated a decreased cell survival, increased mortality, decreased heart weight, and increased ascites in the doxorubicin‐treated groups compared to the control groups. The combined treatment of resveratrol and doxorubicin showed an opposite pattern than the doxorubicin‐treated groups alone. Furthermore, this chemotherapeutic agent induced the biochemical and histopathological changes on the cardiac cells/tissue; however, the results (for most of the cases) revealed that these alterations induced by doxorubicin were reversed near to normal levels (control groups) by resveratrol coadministration. Conclusion. The results of this systematic review stated that coadministration of resveratrol alleviates the doxorubicin‐induced cardiotoxicity. Resveratrol exerts these chemoprotective effects through several main mechanisms of antioxidant, antiapoptosis, and anti‐inflammatory.
Immunotherapy has revolutionized the conventional treatment approaches for colorectal cancer (CRC), offering new therapeutic prospects for patients. Liquid biopsy has shown significant potential in early screening, diagnosis, and postoperative monitoring by analyzing circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). In the era of immunotherapy, liquid biopsy provides additional possibilities for guiding immune-based treatments. Emerging technologies such as mass spectrometry-based detection of neoantigens and flow cytometry-based T cell sorting offer new tools for liquid biopsy, aiming to optimize immune therapy strategies. The integration of liquid biopsy with immunotherapy holds promise for improving treatment outcomes in colorectal cancer patients, enabling breakthroughs in early diagnosis and treatment, and providing patients with more personalized, precise, and effective treatment strategies.
The metabolism of tumors and immune cells in the tumor microenvironment (TME) can affect the fate of cancer and immune responses. Metabolic reprogramming can occur following the activation of metabolic-related signaling pathways, such as phosphoinositide 3-kinases (PI3Ks) and the mammalian target of rapamycin (mTOR). Moreover, various tumor-derived immunosuppressive metabolites following metabolic reprogramming also affect antitumor immune responses. Evidence shows that intervention in the metabolic pathways of tumors or immune cells can be an attractive and novel treatment option for cancer. For instance, administrating inhibitors of various signaling pathways, such as phosphoinositide 3-kinases (PI3Ks), can improve T cell-mediated antitumor immune responses. However, dual pathway inhibitors can significantly suppress tumor growth more than they inhibit each pathway separately. This review discusses the latest metabolic interventions by dual pathway inhibitors as well as the advantages and disadvantages of this therapeutic approach.