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Abstract Title:

Cytotoxic effects of haplamine and its major metabolites on human cancer cell lines.

Abstract Source:

Planta Med. 2008 Aug;74(10):1265-8. Epub 2008 Jul 29. PMID: 18666046

Abstract Author(s):

Sompheary Ea, Sarah Giacometti, Joseph Ciccolini, Valentina Akhmedjanova, Claude Aubert

Abstract:

Haplamine, extracted from Haplophyllum perforatum, is widely used in Central Asia for treating various diseases, including testicular cancer. The purpose of the present study was to investigate in vitro the cytotoxic properties of haplamine and its major metabolites (trans/cis-3,4-dihydroxyhaplamine) on human pancreatic cancer, colorectal cancer and hepatic cancer cell lines. The efficacy of haplamine was compared with those of the respective reference drugs for treating digestive cancers (e. g., 5-FU, gemcitabine). Finally, the implication of apoptosis in haplamine-induced cell death was investigated. The IC50 values of of haplamine were 52.5 +/- 2.6, 24.3 +/- 0.7; 41.5 +/- 2.5, 72 +/- 2, 32 +/- 2.2 and 59.7 +/- 2.1 microM in human pancreatic cancer (Capan1 and Capan2), colorectal cancer (LS174T, HT29, and SW620) and hepatic cancer (HepG2) cells, respectively. The IC50 values of trans/cis-3,4-dihydroxyhaplamine were both > 200 microM, thus suggesting that the previously reported cytotoxic efficacy of haplamine was supported by the parent drug only. Besides, our data showed that haplamine leads to cell death through the induction of early/late apoptosis in the target cells. Interestingly, we found that haplamine showed significant antiproliferative efficacy on resistant SW620 colorectal cells, whereas the reference drug 5-FU was ineffective (32 vs. 73 microM, p < 0.01 t- test), thus suggesting that haplamine could be of interest for treating digestive cancers resistant to standard fluoropyrimidines. Similarly, haplamine proved to be significantly more potent in pancreatic cells than gemcitabine, the reference cytotoxic drug for treating pancreatic carcinomas. Overall, these results confirm the anticancer properties of haplamine suggested by its traditional use, and indicate that it could be further considered in various other solid tumours frequently encountered in adults, including those resistant to standard chemotherapy.

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Sayer Ji
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