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Review
. 2017 Jun 12;9(6):1477-1536.
doi: 10.18632/aging.101250.

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

James A McCubrey  1 , Kvin Lertpiriyapong  2 , Linda S Steelman  1 , Steve L Abrams  1 , Li V Yang  3 , Ramiro M Murata  1   4 , Pedro L Rosalen  5 , Aurora Scalisi  6 , Luca M Neri  7 , Lucio Cocco  8 , Stefano Ratti  8 , Alberto M Martelli  8 , Piotr Laidler  9 , Joanna Dulińska-Litewka  9 , Dariusz Rakus  10 , Agnieszka Gizak  10 , Paolo Lombardi  11 , Ferdinando Nicoletti  12 , Saverio Candido  12 , Massimo Libra  12 , Giuseppe Montalto  13   14 , Melchiorre Cervello  14
Affiliations
Review

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

James A McCubrey et al. Aging (Albany NY). .

Abstract

Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

Keywords: CSCs; SIRT; curcumin; gene methylation; miRs; natural products; resveratrol.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no conflicts of interest with publication of this manuscript.

Figures

Figure 1
Figure 1. Pleiotropic effects of resveratrol on signaling pathways involved in cell growth
Some of the pathways affected by RES are indicated. This diagram focusses on signaling pathways predominately involved in aging and cancer. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 2
Figure 2. Pleiotropic effects of curcumin on signaling pathways involved in cell growth
Curcumin can induce many pathways which may result in suppression of cell growth, induction of apoptosis, autophagy, senescence or inhibition of cell cycle progression. These events are indicated by red arrows. In addition, CUR treatment can result in the suppression of many important proteins which result in decreased growth, EMT, metastasis or inflammation. These events are indicated by black closed arrows.
Figure 3
Figure 3. Effects of curcumin on TP53 and apoptosis pathways
An overview of the effects of CUR on TP53 and apoptotic pathways and the effects of miRs are indicated. miRs in magenta font indicate oncomirs. miRs in blue font are tumor suppressor miRs. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 4
Figure 4. Effects of curcumin on chromatin structure
An overview of the effects of CUR on demethylation of genes and the effects on the various genes are indicated. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event. M = methylation of a sequence.
Figure 5
Figure 5. Effects of curcumin on drug sensitivity pathways
An overview of the effects of CUR on drug sensitivity pathways and the effects of miRs are indicated. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 6
Figure 6. Overview of effect of curcumin on stemness, microenvironment and EMT
An overview of the effects of CUR on pathways involving stemness, microenvironment and EMT pathways and the effects of miRs are indicated. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 7
Figure 7. Effects of curcumin on CRC chemoresistance
An overview of the effects of CUR on CRC chemoresistance and the effects of miRs are indicated. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 8
Figure 8. Effects of curcumin on HCC
An overview of the effects of CUR on HCC is presented. M = methylated residue, A = acetlylated residue. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 9
Figure 9
Overview of effects of curcumin on HIF-1alpha, miRs and metastasis. An overview of the effects of CUR on pathways involving migration, invasion and metastatic pathways are indicated. Red arrows indicate induction of an event; black closed arrows indicate suppression of an event.
Figure 10
Figure 10. Pleiotropic effects of berberine on signaling pathways involved in cell growth
BBRs can induce many pathways which may result in suppression of cell growth, induction of apoptosis, autophagy, senescence, DNA double strand breaks or inhibition of cell cycle progression and DNA replication. These events are indicated by red arrows. In addition, BBR treatment can result in the suppression of many important proteins leading to decreased growth, decreased DNA synthesis, mitochondrial membrane potential, cell cycle arrest and inflammation indicated in black closed arrows.
Figure 11
Figure 11. Effects of berberine on TP53, miRs, apoptosis and drug resistance
Berberine can induce the expression of TP53 and miRs which can alter the expression of many genes involved in the regulation of apoptosis, cell cycle progression and drug resistance. miRs which are oncomirs are indicated in maroon, miRs which are tumor suppressor miRs are indicated in blue.
Figure 12
Figure 12. Chemical structures of modified berberines from naxospharma
See this image and copyright information in PMC

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