New mechanisms and therapeutic potential of curcumin for colorectal cancer

Abstract

Curcumin is a polyphenol derived from Curcuma longa. Over the last few years, a number of studies have provided evidence of its main pharmacological properties including chemosensitizing, radiosensitizing, wound healing activities, antimicrobial, antiviral, antifungical, immunomodulatory, antioxidant and anti-inflammatory. More recent data provide interesting insights into the effect of this compound on cancer chemoprevention and chemotherapy. In fact, preclinical studies have shown its ability to inhibit carcinogenesis in various types of cancer including colorectal cancer (CRC). Curcumin has the capacity of interact with multiple molecular targets affecting the multistep process of carcinogenesis. Also, curcumin is able to arrest the cell cycle, to inhibit the inflammatory response and the oxidative stress and to induce apoptosis in cancer cells. Likewise, it has been shown to possess marked antiangiogenic properties. Furthermore, curcumin potentiates the growth inhibitory effect of cyclo-oxygenase (COX)-2 inhibitors and traditional chemotherapy agents implicating another promising therapy regimen in the future treatment of CRC. However, its clinical advance has been hindered by its short biological half-life and low bioavailability after oral administration. This review is intended to provide the reader an update of the bioavailability and pharmacokinetics of curcumin and describes the recently identified molecular pathways responsible of its anticancer potential in CRC.

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…Curcumin formulated in pills is therefore highly suitable for the treatment of gastrointestinal malignancies (Sharma et al, 2001;Garcea et al, 2005;Villegas et al, 2008) and for long-term chemopreventive therapy (Anto et al, 1996a;Perkins et al, 2002;Lao et al, 2006;Villegas et al, 2008), particularly in the gastrointestinal tract (Huang et al, 1994;Rao et al, 1995), but ill-suited for the treatment of cancers outside of the gastrointestinal system. For these reasons, curcumin for oral chemotherapy of nongastrointestinal cancers should at least be coadministered with uptakeenhancing agents such as piperine (Shoba et al, 1998;Singh et al, 2013) and turmerones (Yue et al, 2012) or in nanoparticle-encapsulated form (Shaikh et al, 2009) when systemic delivery by a (targeted) drug delivery system is not possible (section II.C.2.a.i).…”

“…11 and Supplemental Table 2). Curcumin is ineffectively transported across the intestinal mucosa into the circulation (Holder et al, 1978;Wahlstrom and Blennow, 1978;Ravindranath and Chandrasekhara, 1980;Cheng et al, 2001;Sharma et al, 2001Sharma et al, , 2004Garcea et al, 2004Garcea et al, , 2005Yang et al, 2007a;Vareed et al, 2008;Villegas et al, 2008;Suresh and Srinivasan, 2010;Wahlang et al, 2011;Berginc et al, 2012). Furthermore, the curcumin molecules that bypass transport hurdles and escape biotransformation in the intestinal mucosa (Ireson et al, 2002;Hoehle et al, 2007;Wahlang et al, 2011;Berginc et al, 2012;Dempe et al, 2012), i.e., by definition the first pass effect for orally administered curcumin, and manage to reach the circulation instantaneously become susceptible to chemical modification in blood ; uptake and biotransformation by the liver (second pass effect), kidneys, and other organs (Holder et al, 1978;Wahlstrom and Blennow, 1978;Pan et al, 1999;Asai and Miyazawa, 2000;Garcea et al, 2004;Hoehle et al, 2006;Tamvakopoulos et al, 2007b;Vareed et al, 2008;Marczylo et al, 2009), and excretion via the biliary or urinary system, albeit the latter occurs to a limited extent (Holder et al, 1978;Ravindranath and Chandrasekhara, 1980;Sharma et al, 2004;Marczylo et al, 2009;Suresh and Srinivasan, 201...…”

Inhibitory Effect of Curcumin on IMP Dehydrogenase, the Target for Anticancer and Antiviral Chemotherapy Agents

“…18,19) This is close to a putative efficacious clinical dose of curcumin of 1.2-1.8 g/d in humans. 20) Thus, the curcumin level achieved in the intestinal tract by an oral administration appears to be enough to inhibit the IMPDH activity, but not enough to affect the serum level. The concentration of polyphenols examined was 100 mM.…”

Lunasin: A promising polypeptide for the prevention and treatment of cancer

“…Therefore, anti-inflammation or antioxidation may be an important intervention strategy for the prevention and treatment of cancer (56). Lunasin was demonstrated to exhibit certain anti-inflammatory effects.…”