Review ArticleDigestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives
Introduction
Increased fruit and vegetable consumption has been associated with a decreased cancer risk [1], [2], [3], [4], intensifying interest in plant food phytochemicals as potential physiologically active agents. Chlorophyll is the most ubiquitous of all natural pigments, reaching levels that can exceed 1000 to 2000 ppm wet weight in some species [5], and is responsible for the color of all green plants [6]. Considering the primary role of chlorophyll in photosynthesis and its close association with yellow/orange carotenoid pigments well known for their bioactivity, these blue-green pigments have often been overlooked with regard to their potential physiological impact and role in the prevention of chronic disease.
Chlorophyll and its various derivatives have a long-established history of use in traditional medicine and for therapeutic purposes [7]. Both natural chlorophyll and commercial-grade derivatives such as sodium copper chlorophyllin (SCC) have been widely investigated for a range of beneficial biological activities including wound healing [8], anti-inflammatory properties [9], [10], control of calcium oxalate crystals [11], and internal deodorization [12]. Furthermore, the ability of both natural and commercial chlorophyll derivatives to act as photosensitizers have enabled their utilization as effective agents in photodynamic therapy of cancer [13], [14], [15].
Although these applications illustrate the potential usefulness of chlorophyll derivatives in medical applications, it is perhaps the potential role of these pigments in the prevention of human cancers that has drawn more recent attention. Both SCC and natural chlorophyll derivatives have demonstrated significant biological activities in vitro and in vivo consistent with the prevention of cancer including antioxidant activity, antimutagenic activity, modulation of xenobiotic metabolizing enzymes, and induction of apoptotic events in cancer cell lines. These encouraging results have led to the investigation of chemopreventative effects in humans [16], [17] and further stimulated interest in the absorption and potential tissue distribution of these pigments in humans. Although traditionally assumed to be unabsorbable by humans, limited research efforts have begun to offer evidence supporting the notion that chlorophyll derivatives may in fact be bioavailable. These efforts remain critically important to better understand the mechanism by which dietary chlorophyll derivatives may prevent cancer.
The purpose of this review is to summarize information from relevant scientific studies covering chlorophyll structure; the impact of food processing and digestive conditions; the potential for intestinal uptake and bioavailability; and cancer preventative activities including antioxidant and antimutagenic activity, modulation of xenobiotic metabolism, and induction of apoptosis. Furthermore, an effort is made to further elaborate the differences between research on natural chlorophylls and studies focused on commercially derived semisynthetic derivatives such as SCC.
Section snippets
Chlorophyll structure, stability, and derivatives
Structurally, chlorophyll is a substituted tetrapyrrole with a centrally bound magnesium atom (Fig. 1). The porphyrin macrocycle is further esterified to a diterpene alcohol, phytol, to form chlorophyll. In nature, chlorophyll a and b predominate in higher plants, whereas chlorophyll c, d, and e derivatives are found throughout various photosynthetic algae and diatomic species including brown, red, and yellow-green algae [6]. Furthermore, several additional classes of bacteriochlorophylls, not
Digestive behavior and bioavailability of chlorophyll derivatives
Bioavailability refers to the fraction of any compound ingested and made available for utilization, metabolism, and/or storage by the organism. Information on the bioavailability of chlorophyll derivatives is limited partially because of the general assumption that chlorophyll is unabsorbable by humans. However, considering the natural abundance of chlorophyll in fruit and vegetable tissues, the diversity of derivatives formed through food processing and preparation, and the growing use of
Chlorophyll and cancer prevention
The association of diets rich in phytochemicals with the prevention of cancer has intensified interest in chlorophyll as a class of plant pigments with potential chemopreventative effects. Considering the traditional use of chlorophyll derivatives in medicine [7] and the low toxicity [41], these pigments serve as attractive cancer preventative and potentially therapeutic agents. Research highlighting the bioactivity of chlorophyll in vitro and in vivo as well as potential mechanisms of cancer
Potential mechanism of chlorophyll cancer preventative activity
Several studies have been conducted to elucidate specific mechanisms responsible for the observed cancer preventative activity of chlorophyll derivatives. Focused on in vitro and cell culture–based assays, these efforts have primarily highlighted antioxidant activity, mutagen trapping, modulation of detoxification pathways, and induction of apoptosis as modes of actions responsible, in part, for chlorophyll's protective effects in vivo (Fig. 4).
Conclusions and future directions
Chlorophylls belong to a larger class of phytochemical plant pigments implicated as cancer preventative agents. Investigations highlighting specific derivatives (chlorophylls, pheophorbides, pheophytins, and chlorins), preparations (vegetables, vegetable extracts, and SCC), and protective actions have been reported in the literature. Following the common assumption that chlorophyll is unabsorbable by humans and the strong data to indicate antimutagenic activity in vitro, a central hypothesis
Acknowledgment
The authors thank Rodney Green for assistance in preparation of this manuscript.
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