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

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.

scholarly journals Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Qian Liu ◽  
Elizabeth J Osterlund ◽  
Xiaoke Chi ◽  
Justin Pogmore ◽  
Brian Leber ◽  
...  
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Live Cells ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Anti Cancer ◽  
Apoptotic Proteins ◽  
Binding Interfaces ◽  
Quantifying In ◽  
Bh3 Mimetic

Tumor initiation, progression and resistance to chemotherapy rely on cancer cells bypassing programmed cell death by apoptosis. We report that unlike other pro-apoptotic proteins, Bim contains two distinct binding sites for the anti-apoptotic proteins Bcl-XL and Bcl-2. These include the BH3 sequence shared with other pro-apoptotic proteins and an unexpected sequence located near the Bim carboxyl-terminus (residues 181–192). Using automated Fluorescence Lifetime Imaging Microscopy - Fluorescence Resonance Energy Transfer (FLIM-FRET) we show that the two binding interfaces enable Bim to double-bolt lock Bcl-XL and Bcl-2 in complexes resistant to displacement by BH3-mimetic drugs currently in use or being evaluated for cancer therapy. Quantifying in live cells the contributions of individual amino acids revealed that residue L185 previously thought involved in binding Bim to membranes, instead contributes to binding to anti-apoptotic proteins. This double-bolt lock mechanism has profound implications for the utility of BH3-mimetics as drugs. ​

scholarly journals The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux

Oncotarget ◽  
2016 ◽  
Vol 7 (27) ◽  
pp. 42059-42070 ◽  
Author(s):  
Zhou Long ◽  
BaiJun Chen ◽  
Qian Liu ◽  
Jiang Zhao ◽  
ZhenXing Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Autophagic Flux ◽  
Jnk Pathway ◽  
Reverse Mode ◽  
Cancer Cell Death

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

2015 ◽  
Vol 16 (14) ◽  
pp. 6175-6176 ◽  
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

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

2019 ◽  
Vol 55 (30) ◽  
pp. 4407-4410 ◽  
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.

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

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1947 ◽  
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.

Fulvic acid promotes extracellular anti-cancer mediators from RAW 264.7 cells, causing to cancer cell death in vitro

2016 ◽  
Vol 36 ◽  
pp. 241-248 ◽  
Author(s):  
Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽  
Matharage Gayani Dilshara ◽  
Chang-Hee Kang ◽  
Seungheon Lee ◽  
Yung Hyun Choi ◽  
...  
Keyword(s):  
Cell Death ◽  
Fulvic Acid ◽  
Cancer Cell ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Cancer Cell Death ◽  
Anti Cancer

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

2016 ◽  
Vol 397 (7) ◽  
pp. 661-670 ◽  
Author(s):  
Andrey V. Kulikov ◽  
Ekaterina A. Slobodkina ◽  
Andrey V. Alekseev ◽  
Vladimir Gogvadze ◽  
Boris Zhivotovsky
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Intracellular Signaling ◽  
Cardiac Glycosides ◽  
Epidemiological Studies ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Death ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Cardiac Disorders

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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