The Differential Effects Of Phyllanthus Emblica Water Extract On The Chromosomal Instability, Cell Proliferation And Cell Death Between Human Colorectal Adenocarcinoma Cells And Normal Colon Epithelial Cells

Phyllanthus emblica L.(PE) is a fruited plant indigenous throughout India, Sri Lanka,southern China and New Guinea. PE fruit is a rich source of vitamin C, amino acids, mineralsand many known medicinally relevant polyphenols. Previous studies conducted with PE inrodent models well demonstrated that PE possesses antioxidant, antimutagenic, anti-inflammatory and antidiabetic properties, and protection from multiple organs, including brain,heart, liver, kidney, and stomach. Therefore, PE has been widely used in the traditionalmedicine of some Asian countries.Several studies showed that PE significantly inhibits the in vitro proliferation, invasionand metastasis of many tumor cell lines, and does not significantly effect the proliferation ofnormal cells. The in vivo studies revealed that PE significantly decreases the incidence ofmouse skin tumorigenesis induced by cancerogens, and markedly reduces the sizes of inducedtumors and xenograft tumors in mice. These studies revealed that PE possess the selectivecytotoxic effects on tumor cells, however, whether PE possess the selective cytotoxic effects onthe genome of cancer cells remains to be established.This study was aimed to investigate the differential effects of PE (20–160μg/ml) exposure(24–96h) on the chromosomal instability (micronuclei, nucleoplasmic bridges and nuclearbuds), cell proliferation (nuclear division index and the ratio of cytostasis) and cell death(apoptosis and necrosis) of human colorectal adenocarcinoma (COLO320-DM) cells andhuman colorectal normal (NCM460) cells. Moreover, we studied the effects of PE (80and160μg/ml) exposure (24–72h) on the mitotic instability of NCM460cells, including the bio-markers of metaphase misaligned chromosome, ana-telophase lagging&polar chromosome,ana-telophase chromatin bridge and multinucleated cell.The results showed that PE（20–160μg/ml）exposure（24–96h）has ability to increase thechromosomal instability of COLO320-DM cells, and subsequently induce cell cycle arrest andcell death, indicating that PE was a highly efficient anticancer agent. Conversely, PE（20–160μg/ml）exposur（e24–96h）has ability to decrease the chromosomal instability of NCM460cells, and has trends to increase their proliferation and decrease their death, although no significantwas achieved both. Besides, PE（80–160μg/ml）exposure（24–72h）can activates the mitoticspindle assembly checkpoints and thus maintain the mitotic stability effectively. These datademonstrated that PE can not only selectively kill cancer cells and has no damages on normalcells, but also as a highly effective blocking agent for chemoprevention, because overwhelmingevidence confirms that chromosomal instability and mitotic instability erves as a driving forcein tumor initiation.Taken together, this study provide some cytogenetic evidence of the anticancer property ofPE.