Contrasting effects of cardiac glycosides on cisplatin- and etoposide-induced cell death

Abstract Cardiac glycosides (CGs) or cardiotonic steroids, which constitute a group of naturally occurring compounds with a steroid-like structure, can act on Na+/K+-ATPase as a receptor and activate intracellular signaling messengers leading to a variety of cellular responses. Epidemiological studies have revealed that CGs, used for the treatment of cardiac disorders, may also be beneficial as anti-cancer agents. CGs, acting in combination with other chemotherapeutic agents, may significantly alter their efficiency in relation to cancer cell elimination, causing both sensitization and an increase in cancer cell death, and in some cases resistance to chemotherapy. Here we show the ability of CGs to modulate apoptotic response to conventionally used anti-cancer drugs. In combination with etoposide, CGs digoxin may enhance cytotoxic potential, thereby allowing the chemotherapeutic dose to be decreased and minimizing toxicity and adverse reactions. Mechanisms behind this event are discussed.

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Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway

Scientific Reports ◽

10.1038/s41598-020-75140-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Heon-Su Kim ◽

Jung-Soo Suh ◽

Yoon-Kwan Jang ◽

Sang-Hyun Ahn ◽

Ganesan Raja ◽

...

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Ethanol Extract ◽

Live Cells ◽

Diospyros Kaki ◽

Jnk Pathway ◽

Cancer Cell Death ◽

Anti Cancer

Abstract Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent.

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OvirusTdb: A Repository of Oncolytic Viruses used in Cancer Treatment

10.1101/2020.01.08.896720 ◽

2020 ◽

Author(s):

Anjali Lathwal ◽

Rajesh Kumar ◽

Gajendra P.S. Raghava

Keyword(s):

Cancer Treatment ◽

Cancer Cell ◽

Oncolytic Virus ◽

Cancer Cell Line ◽

Chemotherapeutic Agents ◽

Oncolytic Viruses ◽

Virus Species ◽

Cancer Cell Death ◽

Anti Cancer ◽

Fight Against Cancer

AbstractOne of the emerging technologies to fight against cancer is oncolytic virus-based immunotherapy which directly lysis tumor cells. Recently, the FDA approved an oncolytic virus named T-vec for the treatment of melanoma; several hundred other viruses are in clinical trials. In order to facilitate the scientific community to fight against cancer, we build a repository of oncolytic viruses called OvirusTdb (https://webs.iiitd.edu.in/raghava/ovirustdb/). This is a manually curated repository where information is curated from research papers and patents. The current version of the repository maintains comprehensive information on therapeutically important oncolytic viruses with 5927 records where each record has 25 fields such as the virus species, cancer cell line, synergism with anti-cancer drugs, and many more. It stores information on 09 types of DNA and 15 types of RNA viruses; 300 recombinant and 09 wildtype viral strains; tested against 124 cancer types and 427 cancer cell lines. Approximately, 1047 records show improved anti-cancer response using combinatorial approach of chemotherapeutic agents with virus strains. Nearly, 3243 and 1506 records show cancer cell death via apoptosis induction and immune activation, respectively. In summary, a user-friendly web repository of oncolytic viruses for information retrieval and analysis have been developed to facilitate researchers in designing and discovering new oncolytic viruses for effective cancer treatment.

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Cold Physical Plasma in Cancer Therapy: Mechanisms, Signaling, and Immunity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9916796 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Fatemeh Faramarzi ◽

Parisa Zafari ◽

Mina Alimohammadi ◽

Mohammadreza Moonesi ◽

Alireza Rafiei ◽

...

Keyword(s):

Cell Death ◽

Immune System ◽

Cancer Therapy ◽

Plasma Treatment ◽

Tumor Cells ◽

Cancer Cell ◽

Intracellular Signaling ◽

Current Knowledge ◽

Cancer Cell Death ◽

Physical Plasma

Despite recent advances in therapy, cancer still is a devastating and life-threatening disease, motivating novel research lines in oncology. Cold physical plasma, a partially ionized gas, is a new modality in cancer research. Physical plasma produces various physicochemical factors, primarily reactive oxygen and nitrogen species (ROS/RNS), causing cancer cell death when supplied at supraphysiological concentrations. This review outlines the biomedical consequences of plasma treatment in experimental cancer therapy, including cell death modalities. It also summarizes current knowledge on intracellular signaling pathways triggered by plasma treatment to induce cancer cell death. Besides the inactivation of tumor cells, an equally important aspect is the inflammatory context in which cell death occurs to suppress or promote the responses of immune cells. This is mainly governed by the release of damage-associated molecular patterns (DAMPs) to provoke immunogenic cancer cell death (ICD) that, in turn, activates cells of the innate immune system to promote adaptive antitumor immunity. The pivotal role of the immune system in cancer treatment, in general, is highlighted by many clinical trials and success stories on using checkpoint immunotherapy. Hence, the potential of plasma treatment to induce ICD in tumor cells to promote immunity targeting cancer lesions systemically is also discussed.

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Combining chemotherapeutic agents and netrin‐1 interference potentiates cancer cell death

EMBO Molecular Medicine ◽

10.1002/emmm.201302654 ◽

2013 ◽

Vol 5 (12) ◽

pp. 1821-1834 ◽

Cited By ~ 22

Author(s):

Andrea Paradisi ◽

Marion Creveaux ◽

Benjamin Gibert ◽

Guillaume Devailly ◽

Emeline Redoulez ◽

...

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Chemotherapeutic Agents ◽

Cancer Cell Death

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Role of autophagy in regulation of cancer cell death/apoptosis during anti-cancer therapy: focus on autophagy flux blockade

Archives of Pharmacal Research ◽

10.1007/s12272-020-01239-w ◽

2020 ◽

Vol 43 (5) ◽

pp. 475-488 ◽

Cited By ~ 2

Author(s):

Nirmala Tilija Pun ◽

Won-Jun Jang ◽

Chul-Ho Jeong

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Cancer Cell ◽

Autophagy Flux ◽

Cancer Cell Death ◽

Anti Cancer

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Studies on cancer cell death through delivery of Dopamine as anti-cancer drug by a newly functionalized cobalt ferrite nano-carrier

Colloids and Surfaces A Physicochemical and Engineering Aspects ◽

10.1016/j.colsurfa.2021.127202 ◽

2021 ◽

pp. 127202

Author(s):

Debarati De ◽

Priyanka Upadhyay ◽

Arpita Das ◽

Ajay Ghosh ◽

Arghya Adhikary ◽

...

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Cobalt Ferrite ◽

Cancer Drug ◽

Cancer Cell Death ◽

Anti Cancer

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Anti-Cancer Natural Products Inducing Cross-talk between Apoptosis and Autophagy Mutual Proteins to Regulate Cancer Cell Death: Design of Future Green Anticancer Therapies

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2015.16.14.6175 ◽

2015 ◽

Vol 16 (14) ◽

pp. 6175-6176 ◽

Cited By ~ 3

Author(s):

Soundararajan Vijayarathna ◽

Subramanion L Jothy ◽

Yeng Chen ◽

Jagat R Kanwar ◽

Sreenivasan Sasidharan

Keyword(s):

Cell Death ◽

Natural Products ◽

Cancer Cell ◽

Cross Talk ◽

Cancer Cell Death ◽

Anti Cancer

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Activity-based protein profiling reveals GSTO1 as the covalent target of piperlongumine and a promising target for combination therapy for cancer

Chemical Communications ◽

10.1039/c9cc00917e ◽

2019 ◽

Vol 55 (30) ◽

pp. 4407-4410 ◽

Cited By ~ 6

Author(s):

Li Li ◽

Yue Zhao ◽

Ran Cao ◽

Lin Li ◽

Gaihong Cai ◽

...

Keyword(s):

Cell Death ◽

Combination Therapy ◽

Synergistic Effect ◽

Cancer Cell ◽

Broad Spectrum ◽

Protein Profiling ◽

Cancer Cell Death ◽

Promising Target ◽

Anti Cancer

Through ABPP, piperlongumine was identified to induce cancer cell death by covalently binding and inhibiting GSTO1 and has a broad spectrum synergistic effect with other anti-cancer agents.

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A Stilbenoid Isorhapontigenin as a Potential Anti-Cancer Agent against Breast Cancer through Inhibiting Sphingosine Kinases/Tubulin Stabilization

Cancers ◽

10.3390/cancers11121947 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1947 ◽

Cited By ~ 5

Author(s):

Lalita Subedi ◽

Mahesh Kumar Teli ◽

Jae Hyuk Lee ◽

Bhakta Prasad Gaire ◽

Mi-hyun Kim ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cell Cycle ◽

Cell Death ◽

Cell Growth ◽

Cancer Cell ◽

Mcf7 Cells ◽

Cancer Cell Death ◽

Cycle Arrest ◽

Anti Cancer

Isorhapontigenin (ISO), a tetrahydroxylated stilbenoid, is an analog of resveratrol (Rsv). The various biological activities of Rsv and its derivatives have been previously reported in the context of both cancer and inflammation. However, the anti-cancer effect of ISO against breast cancer has not been well established, despite being an orally bioavailable dietary polyphenol. In this study, we determine the anti-cancer effects of ISO against breast cancer using MCF7, T47D, and MDA-MB-231 cell lines. We observed that ISO induces breast cancer cell death, cell cycle arrest, oxidative stress, and the inhibition of cell proliferation. Additionally, sphingosine kinase inhibition by ISO controlled tubulin polymerization and cancer cell growth by regulating MAPK/PI3K-mediated cell cycle arrest in MCF7 cells. Interestingly, SPHK1/2 gene silencing increased oxidative stress, cell death, and tubulin destabilization in MCF7 cells. This suggests that the anti-cancer effect of ISO can be regulated by SPHK/tubulin destabilization pathways. Overall, ISO successfully induced breast cancer cell death and cell growth arrest, suggesting this phytochemical is a better alternative for breast cancer treatment. Further studies in animal models could confirm the potency and usability of ISO over Rsv for targeting breast cancer, potentially posing an alternative candidate for improved therapy in the near future.

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