scholarly journals New Insights into Curcumin- and Resveratrol-Mediated Anti-Cancer Effects

2021 ◽  
Vol 14 (11) ◽  
pp. 1068
Author(s):  
Andrea Arena ◽  
Maria Anele Romeo ◽  
Rossella Benedetti ◽  
Laura Masuelli ◽  
Roberto Bei ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Cytotoxic Effects ◽  
Anti Cancer ◽  
Cancer Cell Survival ◽  
Anti Oxidant ◽  
Her 2

Curcumin and resveratrol are bioactive natural compounds displaying anti-inflammatory, anti-oxidant and anti-cancer properties. In this study, we compared the cytotoxic effects of these molecules and the molecular mechanisms involved against Her-2/neu-positive breast and salivary cancer cell lines. We found that both curcumin and resveratrol were efficient in reducing cancer cell survival and that they differently affected autophagy, ROS and activation of the PI3K/AKT/mTOR pathway. Moreover, we found that resveratrol and curcumin in combination exerted a stronger cytotoxic effect in correlation with the induction of a stronger ER stress and the upregulation of pro-death UPR molecule CHOP. This effect also correlated with the induction of pro-survival autophagy by curcumin and its inhibition by resveratrol. In conclusion, this study unveils new molecular mechanisms underlying the anti-cancer effects of resveratrol, curcumin and their combination, which can help to design new therapeutic strategies based on the use of these polyphenols.

scholarly journals LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival

Oncogenesis ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Yu Geon Lee ◽  
Hui Won Kim ◽  
Yeji Nam ◽  
Kyeong Jin Shin ◽  
Yu Jin Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Cell Survival ◽  
Cancer Cell ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Tca Cycle ◽  
Mitochondrial Matrix ◽  
Mitochondrial Functions ◽  
Cancer Cell Survival

AbstractMitochondrial proteases are key components in mitochondrial stress responses that maintain proteostasis and mitochondrial integrity in harsh environmental conditions, which leads to the acquisition of aggressive phenotypes, including chemoresistance and metastasis. However, the molecular mechanisms and exact role of mitochondrial proteases in cancer remain largely unexplored. Here, we identified functional crosstalk between LONP1 and ClpP, which are two mitochondrial matrix proteases that cooperate to attenuate proteotoxic stress and protect mitochondrial functions for cancer cell survival. LONP1 and ClpP genes closely localized on chromosome 19 and were co-expressed at high levels in most human cancers. Depletion of both genes synergistically attenuated cancer cell growth and induced cell death due to impaired mitochondrial functions and increased oxidative stress. Using mitochondrial matrix proteomic analysis with an engineered peroxidase (APEX)-mediated proximity biotinylation method, we identified the specific target substrates of these proteases, which were crucial components of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and amino acid and lipid metabolism. Furthermore, we found that LONP1 and ClpP shared many substrates, including serine hydroxymethyltransferase 2 (SHMT2). Inhibition of both LONP1 and ClpP additively increased the amount of unfolded SHMT2 protein and enhanced sensitivity to SHMT2 inhibitor, resulting in significantly reduced cell growth and increased cell death under metabolic stress. Additionally, prostate cancer patients with higher LONP1 and ClpP expression exhibited poorer survival. These results suggest that interventions targeting the mitochondrial proteostasis network via LONP1 and ClpP could be potential therapeutic strategies for cancer.

Abstract 163: Investigation of molecular mechanisms by which PCA3 modulates prostate cancer cell survival

2015 ◽  
Author(s):  
Ana Emilia Goulart ◽  
Luciana B. Ferreira ◽  
Paula Priscilla de Freitas ◽  
Nadia Batoreu ◽  
MARTIN H. BONAMINO ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Prostate Cancer Cell ◽  
Cancer Cell Survival

scholarly journals Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved

2021 ◽  
Vol 22 (19) ◽  
pp. 10874
Author(s):  
Sepideh Bastani ◽  
Moloud Akbarzadeh ◽  
Yeganeh Rastgar Rezaei ◽  
Ali Farzane ◽  
Mohammad Nouri ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cell Survival ◽  
Therapeutic Agent ◽  
Therapeutic Strategies ◽  
Cancer Development ◽  
Seasonal Reproduction ◽  
Anti Cancer ◽  
Promote Cell Survival ◽  
Cancer Cell Survival ◽  
Regulation Of Growth

Hypoxia has an important role in tumor progression via the up-regulation of growth factors and cellular adaptation genes. These changes promote cell survival, proliferation, invasion, metastasis, angiogenesis, and energy metabolism in favor of cancer development. Hypoxia also plays a central role in determining the resistance of tumors to chemotherapy. Hypoxia of the tumor microenvironment provides an opportunity to develop new therapeutic strategies that may selectively induce apoptosis of the hypoxic cancer cells. Melatonin is well known for its role in the regulation of circadian rhythms and seasonal reproduction. Numerous studies have also documented the anti-cancer properties of melatonin, including anti-proliferation, anti-angiogenesis, and apoptosis promotion. In this paper, we hypothesized that melatonin exerts anti-cancer effects by inhibiting hypoxia-induced pathways. Considering this action, co-administration of melatonin in combination with other therapeutic medications might increase the effectiveness of anti-cancer drugs. In this review, we discussed the possible signaling pathways by which melatonin inhibits hypoxia-induced cancer cell survival, invasion, migration, and metabolism, as well as tumor angiogenesis.

scholarly journals Gastric tumorigenesis induced either by Helicobacter pylori infection or chronic alcohol consumption through IL-10 inhibition

2020 ◽  
Author(s):  
Faisal Aziz ◽  
Abhijit Chakarobaty ◽  
Kandong Liu ◽  
Hisae Yoshitomi ◽  
Xiang Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alcohol Consumption ◽  
Mitochondrial Dysfunction ◽  
Cell Survival ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Gastric Carcinogenesis ◽  
Cd8 Cells ◽  
Cancer Cell Survival ◽  
H Pylori

Abstract Background Alcohol is class 1 carcinogen and results in 3.3 million deaths every year. H. pylori is also an important factor for gastric carcinogen. Alcohol consumption is emerging as an important contributor to gastric cancer, but there is no direct or experimental evidence of alcohol and H. pylori infection produce gastric cancer in human and animal model alone. Here, we provide insight into the molecular mechanisms driving gastric carcinogenesis. Results Alcohol consumption, together with H. pylori infection, causes gastric cancer; interleukin-10 (IL-10) downregulation and mitochondrial metabolic dysfunction in CD8+ cells are also involved. IL-10 knockout accelerates tumor development in mice with either H. pylori infection or alcohol induced gastric cancer or both. IL-10 downregulation and CD-8+ cell dysfunction stimulates IL-1β secretion. Specifically, we show IL-10 inhibits glucose uptake and glycolysis and promotes oxidative phosphorylation with lactate inhibition. Consequently, In the absence of IL-10 signaling, CD8+ cells accumulate damaged mitochondria in a mouse model of gastric cancer induced with the combination of alcohol plus H. pylori infection, and this results in mitochondrial dysfunction and production of IL-1 β. IL-1β promotes H. pylori infection and reduces NKX6.3 gene expression, resulting in increased cancer cell survival and proliferation. Conclusions Overall, the molecular mechanisms of gastric carcinogenesis include IL-10 inhibition resulting in lowered host immunity via mitochondrial dysfunction of CD8+ lymphocytes; gastric inflammation due to H. pylori infection, alcohol intake, and IL-1β production; and disruption of gastric-specific tumor suppressor NKX6.3 expression, which increases cancer cell survival and proliferation.

scholarly journals mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression

2018 ◽  
Vol 19 (10) ◽  
pp. 3267 ◽  
Author(s):  
Mio Harachi ◽  
Kenta Masui ◽  
Yukinori Okamura ◽  
Ryota Tsukui ◽  
Paul Mischel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Cancer Cell Survival

Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their survival by enabling cancer cells to obtain the macromolecular precursors and energy needed for the rapid growth. However, an orchestration of appropriate metabolic reactions for the cancer cell survival requires the precise mechanism to sense and harness the nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin (mTOR) complexes are known downstream effectors of many cancer-causing mutations, which are thought to regulate cancer cell survival and growth. Recent studies demonstrate the intriguing role of mTOR to achieve the feat through metabolic reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of metabolism both in normal and cancer cell, but mTORC2, an essential partner of mTORC1 downstream of growth factor receptor signaling, controls cooperatively specific metabolism, which nominates them as an essential regulator of cancer metabolism as well as a promising candidate to garner and convey the nutrient information from the surrounding environment. In this article, we depict the recent findings on the role of mTOR complexes in cancer as a master regulator of cancer metabolism and a potential sensor of nutrients, especially focusing on glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms that amino acids activate mTOR complexes signaling have been identified. We would also like to mention the intricate crosstalk between glucose and amino acid metabolism that ensures the survival of cancer cells, but at the same time it could be exploitable for the novel intervention to target the metabolic vulnerabilities of cancer cells.

Co-targeting EGFR and Autophagy Impairs Ovarian Cancer Cell Survival during Detachment from the ECM

2015 ◽  
Vol 15 (3) ◽  
pp. 215-226 ◽  
Author(s):  
Zongyuan Yang ◽  
Yi Liu ◽  
Xiao Wei ◽  
Xiaoshui Zhou ◽  
Cheng Gong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Survival
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