Cytotoxic and Pro-Apoptotic Properties of Ethyl-p-Methoxycinnamate and Its Hydrophilic Derivative Potassium-p-Methoxycinnamate

Abstract

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.

Interesterification of Egg-Yolk Phosphatidylcholine with p-Methoxycinnamic Acid Catalyzed by Immobilized Lipase B from Candida Antarctica

“…p-MCA HepG2 cell line 27.1 µg/mL (IC 50 ) induction of apoptosis [17] p-MCA Wistar rats 40 mg/kg - [14] Ep-MCA ** DMAB-induced mices 23.4 mg/kg (oil fraction) induction of apoptosis [23] p-MCA HCT-116 cell line 10 µM (IC 50 ) induction of apoptosis [19] Ep-MCA MCF-7 cell line 360 µg/mL (IC 50 ) - [24] Ep-MCA HCT-116 cell line 42 µg/mL (IC 50 ) induction of apoptosis [25] Ep-MCA *** DMH-induced rats 40 mg/kg - [9] * Streptozotocin (STPZ)-induced diabetic rats; ** Mice with colon cancer induced by dimethylbenz(a)anthracene (DMAB) *** Rats with colon cancer induced by dimethylhydrazine (DMH); INS-1, rats pancreatic β-cells; HepG2, human hepatocyte carcinoma cell line; HCT-116, human colon carcinoma cell line; MCF-7, human breast cancer cell lines.…”

Cytotoxicity, Cell Cycle Arrest, and Apoptosis Induction Activity of Ethyl-p-methoxycinnamate in Cholangiocarcinoma Cell

“…Kaempferia galanga Linn. (known as Proh-hom in Thai) exhibits several potential medicinal properties such as analgesic (Sulaiman et al, 2008), anti-inflammatory (Sulaiman, et al, 2008), carminative (Preetha et al, Ethyl-p-methoxycinnamate (EPMC), the major active compound isolated from K. galanga L., exhibits nematicidal (Jae-Kook et al, 2011), antibacterial (Lakshmanan et al, 2011), anti-inflammatory (Umar et al, 2014), and antineoplastic activities (Umar et al, 2018) including inhibition of hepatocellular carcinoma (Liu et al, 2010) and blood vessel formation (He et al, 2012). Based on the information, EPMC might also have anticancer activity in cholangiocarcinoma.…”