Translating Curcumin to the Clinic for Lung Cancer Prevention: Evaluation of the Preclinical Evidence for Its Utility in Primary, Secondary, and Tertiary Prevention Strategies

Howells, Lynne; Mahale, Jagdish; Sale, Stewart; McVeigh, Laura E.; Steward, William P.; Thomas, Anne; Brown, Karen

doi:10.1124/jpet.114.216333

Cited by 24 publications

(15 citation statements)

References 130 publications

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“…However, most of these methods focus on the parent molecule and rarely consider metabolite recovery, stability or specificity. There is tentative evidence suggesting that curcumin may be beneficial in terms of delaying the development of lung cancer in a limited number of animal models (Howells et al, 2014). In order to study the pharmacokinetics and pharmacodynamics of curcumin in the lungs, a robust analytical method is required which allows consistent, reliable and accurate detection of curcumin and its metabolites not only in the plasma but also in lung tissue.…”

Section: Introductionmentioning

confidence: 99%

An HPLC‐UV method for the simultaneous quantification of curcumin and its metabolites in plasma and lung tissue: Potential for preclinical applications

Mahale

Howells

Singh

et al. 2018

Biomedical Chromatography

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Curcumin, derived from turmeric, has been extensively investigated for its broad spectrum of biological activities. Previously reported HPLC-UV methods have focussed on analysis of the parent compound. Here, a sensitive HPLC-UV method was developed and partially validated, then used for the simultaneous determination of curcumin and its glucuronide and sulfate metabolites in plasma and lung tissue from mice. The assay was applied to an in vivo pharmacokinetic study comparing formulated curcumin (Meriva™) with standard curcumin. Plasma levels of glucuronide and sulfate metabolites were 5- and 2-fold higher after Meriva™ administration compared with standard curcumin. In lung tissue, free curcumin was 4-fold higher following Meriva™ administration vs standard curcumin. This assay represents a rapid, cheap method for simultaneous detection of curcumin and its major metabolites that has applicability in pre-clinical settings.

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Section: Introductionmentioning

confidence: 99%

An HPLC‐UV method for the simultaneous quantification of curcumin and its metabolites in plasma and lung tissue: Potential for preclinical applications

Mahale

Howells

Singh

et al. 2018

Biomedical Chromatography

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“…Alternately, prospective recruitment of subjects in clinical trials in addition to integration of recruitment into low dose CT screening programs may offer an excellent venue for approaching high risk subjects, who are motivated by virtue of participation in a screening program. These strategies will ultimately be critical to move this field of chemoprevention forward to prevent lung and other major cancers [41,42]. …”

Section: Discussionmentioning

confidence: 99%

Chemoprevention Trial Feasibility Using Botanicals in Exceptionally High Risk Populations for Lung Cancer

et al. 2014

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While chemoprevention with botanicals shows promise in reducing cancer risk, recruitment and retention of participants for trials continues to be costly and presents unique challenges. Knowledge of interest, willingness of target populations and evaluation of design challenges are critical to improve accrual in these chemoprevention trials. Objective The study assessed interest and willingness of former smokers to participate in a chemoprevention trial using a botanical agent. Methods An introductory letter and survey instrument were mailed to 609 consecutive, former heavy smokers, with no cancer, from a database of 826 subjects at the Moffitt Cancer Center. Results 202 (40.4%) subjects returned completed surveys. 92-96% reported interest in receiving free lung exams and knowing their lung cancer risk. 88% were interested in participating in a trial evaluating a botanical agent for lung cancer prevention. Over 92% of subjects reported willingness to comply with study requirements; multiple blood draws and trips to the Center, spiral CTs and chest x-rays. Subjects were relatively less enthusiastic (73-79%) about bronchoscopy, taking multiple study agents and assignment to placebo arm. Conclusions Our study strongly suggests feasibility, highlights potential challenges and the significant interest and willingness of this exceptionally high risk population to participate in chemoprevention trials.

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“…Using multiple experimental approaches, we tried to address these concerns. We firstly attempted identification of models potentially useful in the lung cancer chemoprevention setting [11], and subsequently generated and applied these models using curcumin as an exemplary agent. We then assessed the effects of long-term, low-dose curcumin intervention and its subsequent withdrawal on lung cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells

et al. 2020

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Curcumin has been investigated extensively for cancer prevention, but it has been proposed that long-term treatments may promote clonal evolution and gain of cellular resistance, potentially rendering cancer cells less sensitive to future therapeutic interventions. Here, we used long-term, low-dose treatments to determine the potential for adverse effects in non-small cell lung cancer (NSCLC) cells. IC50s for curcumin, cisplatin, and pemetrexed in A549, PC9, and PC9ER NSCLC cells were evaluated using growth curves. IC50s were subsequently re-assessed following long-term, low-dose curcumin treatment and a three-month treatment withdrawal period, with a concurrent assessment of oncology-related protein expression. Doublet cisplatin/pemetrexed-resistant cell lines were created and the IC50 for curcumin was determined. Organotypic NSCLC-fibroblast co-culture models were used to assess the effects of curcumin on invasive capacity. Following long-term treatment/treatment withdrawal, there was no significant change in IC50s for the chemotherapy drugs, with chemotherapy-resistant cell lines exhibiting similar sensitivity to curcumin as their non-resistant counterparts. Curcumin (0.25–0.5 µM) was able to inhibit the invasion of both native and chemo-resistant NSCLC cells in the organotypic co-culture model. In summary, long-term curcumin treatment in models of NSCLC neither resulted in the acquisition of pro-carcinogenic phenotypes nor caused resistance to chemotherapy agents.

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Translating Curcumin to the Clinic for Lung Cancer Prevention: Evaluation of the Preclinical Evidence for Its Utility in Primary, Secondary, and Tertiary Prevention Strategies

Cited by 24 publications

References 130 publications

An HPLC‐UV method for the simultaneous quantification of curcumin and its metabolites in plasma and lung tissue: Potential for preclinical applications

An HPLC‐UV method for the simultaneous quantification of curcumin and its metabolites in plasma and lung tissue: Potential for preclinical applications

Chemoprevention Trial Feasibility Using Botanicals in Exceptionally High Risk Populations for Lung Cancer

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells

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