ROS-modulated therapeutic approaches in cancer treatment

Raza, Muhammad Hassan; Siraj, Sami; Arshad, Abida; Waheed, Usman; Aldakheel, Fahad M.; Alduraywish, Shatha A.; Arshad, Muhammad

doi:10.1007/s00432-017-2464-9

Cited by 222 publications

(138 citation statements)

References 200 publications

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“…Agents that increase the levels of ROS in cancer cells lead to cytotoxicity to these cells [39,40]. We assessed the levels of ROS when 122.4 was combined with doxorubicin or etoposide or cisplatin in treating BS-24-1 cells.…”

Section: Resultsmentioning

confidence: 99%

Asteriscus graveolens Extract in Combination with Cisplatin/Etoposide/Doxorubicin Suppresses Lymphoma Cell Growth through Induction of Caspase-3 Dependent Apoptosis

Tayeh

Ofir

2018

IJMS

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Chemotherapy drugs action against cancer is not selective, lead to adverse reactions and drug resistance. Combination therapies have proven more effective in defeating cancers. We hypothesize that plant extract/fraction contains many/several compounds and as such can target multiple pathways as cytotoxic agent and may also have chemo sensitizing activities. We designed a study in which, Asteriscus graveolens (Forssk.) Less (A. graveolens)-derived fraction that contains sesquiterpene lactone asteriscunolide isomers (AS) will be tested in combination with known chemotherapy drugs. Successful combination will permit to reduce chemotherapy drugs concentration and still get the same impact on cancer cells. Sesquiterpene lactone such as asteriscunolide isomers is a naturally occurring compound found in a variety of fruits, vegetables, and medicinal plants with anti-cancer properties. The experiments presented here showed that adding plant fraction containing AS permit reducing the concentration of cisplatin/etoposide/doxorubicin in order to reduce mouse BS-24-1 lymphoma cells (BS-24-1 cells) survival. It involved enhancing the production of Reactive Oxygen Species (ROS), activation of caspase-3 and inhibition of Topoisomerase I activity. Taken together, the results suggest that A. graveolens fraction sensitized BS-24-1 cells to cisplatin/etoposide/doxorubicin through induction of ROS and caspase-3-dependent apoptosis.

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Section: Resultsmentioning

confidence: 99%

Asteriscus graveolens Extract in Combination with Cisplatin/Etoposide/Doxorubicin Suppresses Lymphoma Cell Growth through Induction of Caspase-3 Dependent Apoptosis

Tayeh

Ofir

2018

IJMS

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“…Superoxide is the precursor of ROS and is crucial to the oxidative chain reaction. Hydrogen peroxide is produced when superoxide is dismutated by the enzyme superoxide dismutase [46]. Here, both superoxide and hydrogen peroxide were elevated soon after combined treatment, which thereafter activated the antioxidant system.…”

Section: Discussionmentioning

confidence: 99%

Baicalin Augments Hyperthermia-Induced Apoptosis in U937 Cells and Modulates the MAPK Pathway via ROS Generation

Zakki

Cui

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. Methods: U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO₂ and 95% air. Cell viability was analyzed by Trypan blue exclusion assay. Apoptosis was examined by DNA fragmentation, fluorescence microscopy and flow cytometry. Generation of mitochondrial trans-membrane potential (MMP), mitochondrial calcium, and reactive oxygen species (ROS) was also detected by flow cytometry. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. Results: Hyperthermia alone did not reduce cell viability or induce notable levels of apoptosis, but combined hyperthermia and BCN treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Mitochondrial transmembrane potential was significantly decreased, and generation of reactive oxygen species (ROS) and suppression of antioxidant enzymes were marked. Furthermore, with the combined treatment, the phosphorylated forms of JNK and p38 showed increased expression, whereas AKT was dephosphorylated. JNK-IN-8 (a JNK inhibitor) and NAC (a ROS scavenger) abrogated the apoptotic effects of the combined treatment, significantly protecting the cells and indicating the involvement of high ROS generation and the MAPK pathway in the underlying molecular mechanism. Conclusion: This study provides compelling evidence that hyperthermia, in combination with BCN, is a promising therapeutic strategy for enhancement of apoptosis and suggest a promising therapeutic approach for cancer.

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“…Metal dyshomeostasis and an oxidizing cellular environment are hallmarks of cancer cells (72,73). As a result, substantial research has been dedicated to understanding and manipulating copper in cancer to prevent cancer progression.…”

Section: Controlling Cancer With Labile Coppermentioning

confidence: 99%

Copper signaling in the brain and beyond

Ackerman

Chang

2018

Journal of Biological Chemistry

128

115

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Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition metal signaling, where dynamic changes in transition metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

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ROS-modulated therapeutic approaches in cancer treatment

Cited by 222 publications

References 200 publications

Asteriscus graveolens Extract in Combination with Cisplatin/Etoposide/Doxorubicin Suppresses Lymphoma Cell Growth through Induction of Caspase-3 Dependent Apoptosis

Asteriscus graveolens Extract in Combination with Cisplatin/Etoposide/Doxorubicin Suppresses Lymphoma Cell Growth through Induction of Caspase-3 Dependent Apoptosis

Baicalin Augments Hyperthermia-Induced Apoptosis in U937 Cells and Modulates the MAPK Pathway via ROS Generation

Copper signaling in the brain and beyond

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