Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics

Kirtonia, Anuradha; Gala, Kavita; Fernandes, Stina George; Pandya, Gouri; Pandey, Amit Kumar; Sethi, Gautam; Khattar, Ekta; Garg, Manoj

doi:10.1016/j.semcancer.2020.04.006

Cited by 114 publications

(70 citation statements)

References 306 publications

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“…Chemotherapy is an inevitable part of cancer therapy, but its potential has been restricted in recent years, due to the resistance of cancer cells [ 259 , 260 ]. In fact, chemoresistance of cancer cells has urged scientists to seek new anti-tumor agents [ 261 ]. Based on the role of natural products in cancer treatment, they can be beneficial in sensitizing cancer cells into chemotherapy [ 262 , 263 ].…”

Section: Chrysin Chemotherapy and Drug Resistancementioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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Section: Chrysin Chemotherapy and Drug Resistancementioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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“…This means that about 113.9 million and 493.4 million Chinese adults may suffer from diabetes and prediabetes respectively [2].Diabetic nephropathy(DN), as a microvascular complication of diabetes, is characterized by microalbuminuria, glomerular basement membrane thickening, mesangial matrix expansion and tubulointerstitial fibrosis [3].DN is incurable and often leads to end-stage renal disease(ESRD).However, the pathogenesis of diabetes is still not clear and there are currently no effective treatments to prevent the progression to ESRD. Currently, clinical treatment is mainly focused on the control of blood pressure, blood glucose and inhibition of the renin angiotensin system (RAS) [4].Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blocker (ARB)are blockers of RAS [5]. In cases of DN, combined treatment using ACEI and ARB is more successful in decreasing 24h proteinuria than ACEI alone [6].The American Diabetes Association(ADA) recommends ARB for type 2 DN [7].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of tripterygium glycosides combined with ARB on diabetic nephropathy: a meta-analysis

Huang

Zhang

et al. 2020

Bioscience Reports

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The purpose of this meta-analysis was to evaluate the beneficial and adverse effects of tripterygium glycosides (TG) combined with angiotensin II receptor blocker (ARB) on diabetic nephropathy (DN). We searched for randomized controlled trials (RCTs) in PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chinese Biomedical Literature Database, China Science and Technology Journal Database up to June 2017. Weighted mean difference (WMD) and standardized mean difference (SMD) were used for continuous variables and all variables were expressed by 95 % confidence interval (CI). 23 studies with 1810 DN patients were included in this meta-analysis. TG combined with ARB statistically significantly improved 24 hours urinary total protein (24h UTP) (SMD,-1.46; 95%CI,-1.84 to -1.09; P<0.00001),urinary albumin excretion rate (UAER) (SMD,-6.9; 95%CI,-9.65 to -4.14, P<0.00001),serum creatinine (SCr) (WMD,-7.65.14; 95%CI，-12.99 to -2.31；P=0.005) and albumin (Alb) (WMD, 5.7; 95%CI, 4.44 to 6.96; P<0.00001) more than did ARB alone. TG combined with ARB statistically significantly affected the level of serum glutamic pyruvic transaminase (SGPT) (WMD, 1.08; 95%CI, 0.04 to 2.12, P=0.04) more than did ARB alone. Compared with ARB alone, TG combined with ARB showed no significant difference in improving blood urea nitrogen (BUN) and hemoglobin A1c (HbA1c). Minor side effects from the combined treatment were observed and mainly focused on the abnormal liver function. TG combined with ARB offers a novel concept in treating DN, more high quality RCTs are needed for better understanding and applying of the combined treatment in DN.

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“…Nonetheless, PPARγ activation may not be involved in nootkatone-induced NAG-1 expression at the transcriptional level. Since the emerging pieces of evidence indicate that repurposing of drugs is crucial to the faster and cheaper discovery of anti-cancerous drugs [40], nootkatone should be seriously considered for the design of future cancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

et al. 2020

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Background A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Methods Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Results Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. Conclusion In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.

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Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics

Cited by 114 publications

References 306 publications

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Efficacy of tripterygium glycosides combined with ARB on diabetic nephropathy: a meta-analysis

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

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