Using natural products to promote caspase-8-dependent cancer cell death

Abstract The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patients) are highly resistant to TRAIL-mediated cell death. Therefore, there is an underlying interest in identifying agents that can be combined with TRAIL to improve its efficacy. There are numerous reports in which combination of TRAIL with standard antineoplastic drugs has resulted in enhanced cancer cell death in vitro. However, many of these chemotherapeutic drugs are nonspecific and associated with adverse effects, which raise serious concerns for cancer therapy in patients. By contrast, natural products have been shown to be safer and efficacious alternatives. Recently, a number of studies have suggested that certain natural products when combined with TRAIL can enhance cancer cell death. In this review, we highlight molecular pathways that might be targeted by various natural products to promote cell death, and focus on our recent work with withanolides a...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 14 August 2019Source: Seminars in Cancer BiologyAuthor(s): Dharambir Kashyap, Hardeep Singh Tuli, Mukerrem Betul Yerer, Ajay Sharma, Katrin Sak, Saumya Srivastava, Anjana Pandey, Vivek Kumar Garg, Gautam Sethi, Anupam BishayeeAbstractApplication of natural product-based nanoformulations for the treatment of different human diseases, such as cancer, is an emerging field. The conventional cancer therapeutic modalities, including surgery, chemotherapy, immunotherapy, radiotherapy has limited achievements. A larger number of drawbacks are associated with these therapies, including damage to p...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
It is good to see that more of the promising technical approaches to aspects of aging, originally put forward by people in the SENS rejuvenation research network some years ago, are now making solid progress towards commercial implementation. The LIFT, or GIFT, approach to cancer therapy involves the transplantation of suitably aggressive leukocyte or granulocyte immune cells from a donor. At the time it was first demonstrated to be highly effective in mice, more than a decade ago, the underlying mechanisms were not well explored, and that always makes it hard to obtain further support from scientific funding institutions....
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
ConclusionThese results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsThis study shows the presence of T cell subsets in the tumor micro-environment expressing both activating and inhibitory receptors. These TAI cells can be targeted by combined immunotherapy leading to improved survival.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSION: Based on our series as well as the existing literature demonstrating the use of local therapy for irAEs, we propose an approach to local therapy for cancer therapy-associated uveitis starting with topical steroids and initiating injectable steroids in cases of recalcitrant panuveitis or posterior uveitis. Subclinical inflammation on posterior segment imaging responds robustly to difluprednate or intravitreal steroid therapy, and patients with posterior segment involvement may require more aggressive management and long-term maintenance. PMID: 31409649 [PubMed - as supplied by publisher]
Source: The British Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Br J Ophthalmol Source Type: research
Despite the tremendous progress made in the field of cancer therapy in recent years, certain solid tumors still cannot be successfully treated. Alongside classical treatments in the form of chemotherapy and/or radiotherapy, targeted treatments such as immunotherapy that cause fewer side effects emerge as new options in the clinics. However, these alternative treatments may not be useful for treating all types of cancers, especially for killing infiltrative and circulating tumor cells (CTCs). Recent advances pursue the trapping of these cancer cells within a confined area to facilitate their removal for therapeutic and diag...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract In recent years, immunotherapy has become an innovative technology for cancer therapy with the discovery of immunological checkpoints. It has shown great potential in a variety of advanced cancer treatments. Particularly, significant progress has been achieved in the understanding of programmed death-1/programmed death ligand-1 (PD-1/ PD-L1) pathway. Nivolumab, a human immunoglobulin (Ig)G4 PD-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of advanced non-small-cell lung cancer (NSCLC). Nivolumab has become a mainstay of first-line treatment of advanced/metastatic NSCLC with...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
These small molecules are novel nucleotide derivatives, containing either a purine or pyrimidine nucleobase, that competitively block the enzyme CD73, also known as ecto-5'-nucleotidase. This enzyme converts extracellular AMP (not a potent activator of adenosine receptors) to adenosine (the native activator of 4 subtypes of adenosine receptors. CD73 inhibitors are being used, in clinical trials and preclinical research, in conjunction with cancer immunotherapy. CD73 is upregulated around tumors to produce excessive adenosine, and blocking this enzyme greatly reduces immunosuppressive adenosine in the tumor microenvironment...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
Immunoediting is a well-established concept in oncology, describing the processes by which tumors are selected for resistance to immune-mediated elimination. The recent emergence of immunotherapies, such as checkpoint inhibitors, as pillars of cancer therapy has intensifed interest in immunoediting as a constraint limiting the efficacy of these therapies. Immunoediting manifests at a number of levels for different cancers, for example through the establishment of immunosuppressive microenvironments within solid tumors. Of particular interest to the current review, selection also occurs at the cellular level; and recent stu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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