Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

doi:10.5246/jcps.2016.01.002

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (1): 12-22.DOI: 10.5246/jcps.2016.01.002

• 【传统中药和植物药的癌症预防专栏】 • 上一篇下一篇

Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

Sujit Nair^1*, Ah-Ng Tony Kong^2*

1. Amrita Cancer Discovery Biology Laboratory, Amrita Vishwa Vidyapeetham University, Amritapuri, Clappana P.O., Kollam, Kerala-690525, India
2. Center for Cancer Chemoprevention Research and Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ-08854, US

收稿日期:2015-09-15 修回日期:2015-10-18 出版日期:2016-01-27 发布日期:2015-10-29
通讯作者: E-mail: sujit108@gmail.com, kongt@pharmacy.rutgers.edu
基金资助:
Institutional funds from Amrita Vishwa Vidyapeetham University, India, and Rutgers, the State University of New Jersey, USA; and RO1 CA118947 and RO1 CA152826 from the National Institutes of Health (NIH), USA.

Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

Sujit Nair^1*, Ah-Ng Tony Kong^2*

1. Amrita Cancer Discovery Biology Laboratory, Amrita Vishwa Vidyapeetham University, Amritapuri, Clappana P.O., Kollam, Kerala-690525, India
2. Center for Cancer Chemoprevention Research and Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ-08854, US

Received:2015-09-15 Revised:2015-10-18 Online:2016-01-27 Published:2015-10-29
Contact: E-mail: sujit108@gmail.com, kongt@pharmacy.rutgers.edu
Supported by:
Institutional funds from Amrita Vishwa Vidyapeetham University, India, and Rutgers, the State University of New Jersey, USA; and RO1 CA118947 and RO1 CA152826 from the National Institutes of Health (NIH), USA.

摘要/Abstract

摘要： Sulforaphane (SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapyregimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry.We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceuticalSFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.

关键词: Pharmacometrics, Pharmacokinetics, Quantitative systems pharmacology, Target engagement, Metabolism, Pharmacogenomics, Chemoprevention, Sulforaphane, Isothiocyanate, Prostate cancer

Abstract:

Sulforaphane (SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapyregimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry.We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceuticalSFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.

Key words: Pharmacometrics, Pharmacokinetics, Quantitative systems pharmacology, Target engagement, Metabolism, Pharmacogenomics, Chemoprevention, Sulforaphane, Isothiocyanate, Prostate cancer

中图分类号:

R962

Supporting:

Sujit Nair, Ah-Ng Tony Kong. Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention[J]. 中国药学(英文版), 2016, 25(1): 12-22.

Sujit Nair, Ah-Ng Tony Kong. Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(1): 12-22.

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Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

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