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The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer.
Hu, Y, Guo, N, Yang, T, Yan, J, Wang, W, Li, X
Oxidative medicine and cellular longevity. 2022;:1458143
Abstract
Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well-known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.
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Potential Anticancer Properties and Mechanisms of Action of Formononetin.
Jiang, D, Rasul, A, Batool, R, Sarfraz, I, Hussain, G, Mateen Tahir, M, Qin, T, Selamoglu, Z, Ali, M, Li, J, et al
BioMed research international. 2019;:5854315
Abstract
Nature, a vast reservoir of pharmacologically active molecules, has been most promising source of drug leads for the cure of various pathological conditions. Formononetin is one of the bioactive isoflavones isolated from different plants mainly from Trifolium pratense, Glycine max, Sophora flavescens, Pycnanthus angolensis, and Astragalus membranaceus. Formononetin has been well-documented for its anti-inflammatory, anticancer, and antioxidant properties. Recently anticancer activity of formononetin is widely studied. This review aims to highlight the pharmacological potential of formononetin, thus providing an insight of its status in cancer therapeutics. Formononetin fights progression of cancer via inducing apoptosis, arresting cell cycle, and halting metastasis via targeting various pathways which are generally modulated in several cancers. Although reported data acclaims various biological properties of formononetin, further experimentation on mechanism of its action, medicinal chemistry studies, and preclinical investigations are surely needed to figure out full array of its pharmacological and biological potential.
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Dose-response relation between dietary inflammatory index and human cancer risk: evidence from 44 epidemiologic studies involving 1,082,092 participants.
Li, D, Hao, X, Li, J, Wu, Z, Chen, S, Lin, J, Li, X, Dong, Y, Na, Z, Zhang, Y, et al
The American journal of clinical nutrition. 2018;(3):371-388
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Abstract
BACKGROUND A newly developed dietary inflammatory index (DII) to evaluate the inflammatory potential of diets was published recently. Many studies have investigated the link between diet-related inflammation and human cancer risk, but the results remain controversial. OBJECTIVE We sought to determine the dose-response relation between DII and human cancer risk based on published epidemiologic literature. DESIGN To summarize evidence, we performed a dose-response meta-analysis to investigate the association between DII and cancer incidence. We systematically searched PubMed, Embase, Web of Science, and the Cochrane library up to 5 November 2017. After data extraction, pooled RRs were calculated and dose-response analyses were performed using a restricted cubic spline model with 4 knots. Subgroup analyses, sensitivity analyses, and tests for publication bias were also performed. RESULTS In all, 44 high-quality studies with 1,082,092 participants were included. The results showed that an elevated DII (continuous-RR: 1.13; 95% CI: 1.09, 1.16; category DIIhighest vs lowest-RR: 1.58; 95% CI: 1.45, 1.72) independently indicated higher cancer risk except for lung cancer and Australian studies. A linear dose-response relation between DII and overall cancer risk was found, with an 8.3% increase in the risk of cancer per DII score. The pooled RR of DII and cancer risk was 1.86 (95% CI: 1.63, 2.13) from 30 case-control studies but was lower in 14 prospective cohorts (RR: 1.29; 95% CI: 1.19, 1.40). The sensitivity analysis and Egger's test supported the main results. CONCLUSIONS Our analysis indicated that higher DII is significantly correlated with cancer risk. More prospective studies with large sample sizes, involving more ethnic groups and different cancer types, are required in the future. This review was registered with PROSPERO as CRD42017077075.
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Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations.
Li, D, Du, X, Guo, X, Zhan, L, Li, X, Yin, C, Chen, C, Li, M, Li, B, Yang, H, et al
Journal of experimental & clinical cancer research : CR. 2017;(1):168
Abstract
BACKGROUND Previous studies have indicated that tumor mitochondrial DNA (mtDNA) mutations are primarily shaped by relaxed negative selection, which is contradictory to the critical roles of mtDNA mutations in tumorigenesis. Therefore, we hypothesized that site-specific selection may influence tumor mtDNA mutations. METHODS To test our hypothesis, we developed the largest collection of tumor mtDNA mutations to date and evaluated how natural selection shaped mtDNA mutation patterns. RESULTS Our data demonstrated that both positive and negative selections acted on specific positions or functional units of tumor mtDNAs, although the landscape of these mutations was consistent with the relaxation of negative selection. In particular, mutation rate (mutation number in a region/region bp length) in complex V and tRNA coding regions, especially in ATP8 within complex V and in loop and variable regions within tRNA, were significantly lower than those in other regions. While the mutation rate of most codons and amino acids were consistent with the expectation under neutrality, several codons and amino acids had significantly different rates. Moreover, the mutations under selection were enriched for changes that are predicted to be deleterious, further supporting the evolutionary constraints on these regions. CONCLUSION These results indicate the existence of site-specific selection and imply the important role of the mtDNA mutations at some specific sites in tumor development.
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Plant natural products: from traditional compounds to new emerging drugs in cancer therapy.
Ouyang, L, Luo, Y, Tian, M, Zhang, SY, Lu, R, Wang, JH, Kasimu, R, Li, X
Cell proliferation. 2014;(6):506-15
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Abstract
Natural products are chemical compounds or substances produced naturally by living organisms. With the development of modern technology, more and more plant extracts have been found to be useful to medical practice. Both micromolecules and macromolecules have been reported to have the ability to inhibit tumour progression, a novel weapon to fight cancer by targeting its 10 characteristic hallmarks. In this review, we focus on summarizing plant natural compounds and their derivatives with anti-tumour properties, into categories, according to their potential therapeutic strategies against different types of human cancer. Taken together, we present a well-grounded review of these properties, hoping to shed new light on discovery of novel anti-tumour therapeutic drugs from known plant natural sources.