Phytother Res. Epub Feb Anticancer activity of Morinda citrifolia Noni fruit: a review. Brown AC 1. Botanical and chemical indexes were not included. Of the 19 studies actually related to cancer, seven publications were in vitro cancer studies, nine were in vivo animal cancer studies, and three were in vivo human cancer studies.
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All fungal extracts were tested in triplicate, and IC50 values were calculated from the mean dose-response curves. IC50 values represent the average over triplicate experiments performed with three successive passages of the same endophyte.
Several endophytes were isolated on more than one occasion, with an average of unique endophytes obtained per isolation attempt using both MEA and PDA. Colletotrichum gloeosporioides and C. In addition, all endophytes obtained in this study have previously been reported to exist in endophytic relationships with other host plants.
Molecular Identification of Endophytes The paucity of discriminatory morphological and physiological characteristics for reliable species identification renders genotypic methods superior to phenotypic and biochemical techniques. Indeed, the ITS region of the ribosomal repeat unit has become the primary genetic marker for molecular identification in many groups of fungi [ 22 , 23 ].
BLAST hits were examined critically to isolate published annotations of equivalent read length and uncompromised technical quality. In addition, best matches in similarity sequences were associated with high BLAST quality scores — bits and Expect values of zero.
Published sequences were assigned greater weight as reference sequences. We consistently obtain agreement among the top ranking BLAST matches for each endophyte; this served to increase the confidence level of the taxonomic assignment.
Anamorphic and teleomorphic forms of the endophytes, in addition to synonyms, are frequently represented in the BLAST hit lists.
Despite the rigorous and systematic approach adopted, a few isolates could not be assigned to species level due to the absence of relevant and definitive Genbank records. Furthermore, assignments to species level employing a heuristic search function such as BLAST and a database of nominally curated public sequences cannot be expected to be unambiguous. Species names were avoided except in cases where an overwhelming number of published records suggest a particular fungal individual.
These insertions vary in occurrence within groups and species, and even within an individual fungus [ 25 ]. Cytotoxicity of Noni Juice and Endophytic Fungal Extracts Fermented noni juice, with or without pasteurization, exhibited only weak in vitro cytotoxic effects against the cancer cell lines used in this study. Fresh noni juice itself was also found to be noncytotoxic.
Noni preparations that were not laboratory-processed were deemed to be too dilute to enable the in vitro detection of cytotoxic constituents by cell culture methods. In effect, sugars and other nutritional components in these juice preparations were observed to promote the growth of cultured cancer cells. Table 2. IC50 values obtained were reproducible over three successive passages of the fungi. Morphological Observations of Extract-Treated Cancer Cells The changes in morphology of cancer cells in response to treatment were examined daily using a Zeiss Axiovert inverted microscope x.
LU-1, MCF-7, and PC-3 responded similarly to the endophyte extracts when viewed daily over the course of the 3-day cytotoxicity assay. The magnitude of the global cellular changes increased with the concentration of extract present, and with time of exposure.
Cell shrinkage with increased cytoplasmic granularity was observed 12 hours after plating. Nuclear condensation pyknosis and apoptotic bodies were clearly visible 48 hours after treatment with pronounced lysis occurring on day 3. It is common for cytotoxic natural product extracts to induce apoptotic changes in cultured cells. The morphological changes observed were likely due to the composite effect of uncharacterized metabolites present in each crude endophyte extract on cellular pathways that ultimately led to cell death and disintegration.
While apoptosis is a definitive marker for the presence of cytotoxic constituents, valuable insight into the effect of discrete metabolites on the death pathways can only be achieved with the isolation and characterization of pure fungal constituents. Conclusions Surveys have indicated that plants with ethnomedical significance have a greater likelihood of hosting endophytes that produce pharmacologically interesting natural products [ 26 , 27 ].
Therefore, it stands to reason that the medicinal properties of plants could be due, in part, to their resident endophytes [ 28 ]. Since the recognition that medicinal plants constitute a repository of endophytic fungi that produce novel and pharmaceutically important metabolites, studies on the applied aspects of these relatively cryptic associations have focused on medicinal plants [ 29 , 30 ].
Noni has become pervasive in the thriving market for nutraceuticals. Noni fruit juice is also an established ingredient in CAM approaches for cancer. Our present work will provide the foundation for further inquiry into the plausible role of microbes in the purported pharmacological effects of noni.
A survey of culturable fungal endophytes resident within the noni plant of Hawaii revealed the presence of 11 distinct genera belonging to the Ascomycota in the healthy mature leaves of noni Table 1. Three additional genera occur in noni fruits inclusive of a genus from the Basidiomycota. The small-scale fermentation of malt extract broth by Stemphylium solani, Leptosphaerulina australis, and Xylaria sp.
In addition to the phytochemical isolation of these cytotoxic constituents from large-scale fermentation cultures, the ensuing phase of this study will interrogate the chemical profile of endophyte-fermented noni juice by a reductionist approach.
Fresh noni juice will be filter-sterilized before being inoculated by individual fungus endophyte and subjected to anaerobic fermentation. Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper.
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Anticancer activity of Morinda citrifolia (Noni) fruit: a review.