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Background  This study aims to determine the synergistic effects of the chemotherapeutic drug melphalan and the phytoconstituents extracted from  Pinus kesiya  Royle ex Gordon ( Simaosong ) in human cancer cells.    Methods   P. kesiya  twigs extracted from 50 % ethanol–water were evaluated alone (6–500 µg/mL) and in combination with melphalan (0.75–15 µg/mL). The cytotoxic effects of single extract or extract and melphalan combination were examined by a neutral red assay to investigate their antiproliferative and apoptosis induction effects in the U937 and HepG2 cell lines. Nuclei morphological change and DNA fragmentation were examined by DNA nuclei staining with 4´6-diamidino-2-phenylindole (DAPI) and agarose gel electrophoresis, respectively. The chemical constituents of the  P. kesiya  extract were assessed using gas chromatography–mass spectrometry (GC–MS) analysis. The synergistic effects of different IC 50  ratios of the  P. kesiya  extract and melphalan combination were analyzed in each cancer cell line. The dose reduction index (DRI) was calculated to determine the extent of concentration reduction in the combination treatment compared with the concentration of each single treatment.    Results  The IC 50  ratios for melphalan to  P. kesiya  extract that caused 75 % antiproliferation could be reduced after combination. This response was greater in the U937 cells than in the HepG2 cells (all  P  < 0.001). Melphalan and  P. kesiya  extract had a similar effect on apoptosis induction both singly and in combination.  P. kesiya  extract synergized the antiproliferation and apoptosis induction effects of melphalan.    Conclusions  Combining the  P. kesiya  extract with melphalan reduced toxicity while retaining the therapeutic efficacy of melphalan.

Synergistic effects of melphalan and Pinus kesiya Royle ex Gordon (Simaosong) extracts on apoptosis induction in human cancer cells