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.