Purpose The present study was designed to investigate the underlying mechanism of cytotoxic and pro-apoptotic potential of ethyl-p-methoxycinnamate (EPMC) and its hydrophilic derivative potassium-p-methoxycinnamate (KPMC). Methods EPMC was isolated from Kaempferia galanga extract and its ethyl chain was replaced with potassium by KOH reflux to synthesize KPMC. The anti-proliferative effect of EPMC and KPMC was evaluated in six cancer cell lines and two normal cell lines by MTT assay. The inhibitory effects of the test compounds on colony formation, cell migration, chromatin condensation and mitochondrial membrane potential was further investigated in HCT-116 cells whereas their effect on caspase 3, 7, 8 and 9 activities was studied in HCT-116 and PC-3 cells. Results EPMC exhibited significant antiproliferative effect in all six cancer cell lines with maximum cytotoxicity against HCT-116 cells (selectivity index > 6). Our results showed significant inhibition of cell migration and colony formation in EPMC-treated colorectal carcinoma cells (HCT-116) when compared to the normal colon fibroblasts (CCD-18co). It exhibited dose dependent chromatin condensation and loss of mitochondrial membrane potential with subsequent induction of caspase 3/7 activity. KPMC did not inhibit the proliferation of either cell lines in MTT assay. Moreover, the cell migration, colony formation and caspase induction in KPMC-treated cells was comparable with the negative control. Conclusion The replacement of alkyl chain in EPMC by potassium resulted into the loss of cytotoxic and pro-apoptotic effects of EPMC.