TY - GEN
T1 - Long Chain Alkyl Esters of Hydroxycinnamic Acids as Promising Anticancer Agents
T2 - Selective Induction of Apoptosis in Cancer Cells
AU - Kayani, Zahra
N1 - Funding Information:
The financial support from the Vice Chancellor for Research, Shiraz University of Medical Sciences (Grant numbers 5360 and 94-01-12-11136); University of Aveiro and Goa University for laboratory facilities; Fundaca̧ õ para a Ciencia e a Tecnologia (FCT, Portugal), European Union, QREN, FEDER, and COMPETE for funding the QOPNA and CIQUP research units (projects PEst-C/QUI/UI0062/2013 and UID/QUI/ 00081/2015, POCI-01-0145-FEDER-006980) and research grants for JCJMDS Menezes from QOPNA are gratefully acknowledged.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/8/23
Y1 - 2017/8/23
N2 - Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16, and C18 alkyl esters of p-coumaric, ferulic, sinapic, and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC
50 values of 0.123 ± 0.012, 0.301 ± 0.069 and 1.0 ± 0.1 μM, respectively. Compounds 1c, 1d, and 4c significantly increased apoptotic cells in sub-G1 phase and activated the caspase-3 enzyme in MOLT-4 cells. Compound 1c was 15.4 and 23.6 times more potent than doxorubicin and cisplatin, respectively, against the drug resistant MES-SA-DX5 uterine sarcoma cells. These p-coumarate esters were several times less effective against NIH/3T3 fibroblast cells. Docking studies showed that 1c may cause cytotoxicity by interaction with carbonic anhydrase IX. In conclusion, long chain alkyl esters of p-coumaric acid are promising scaffolds for selective apoptosis induction in cancer cells.
AB - Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16, and C18 alkyl esters of p-coumaric, ferulic, sinapic, and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC
50 values of 0.123 ± 0.012, 0.301 ± 0.069 and 1.0 ± 0.1 μM, respectively. Compounds 1c, 1d, and 4c significantly increased apoptotic cells in sub-G1 phase and activated the caspase-3 enzyme in MOLT-4 cells. Compound 1c was 15.4 and 23.6 times more potent than doxorubicin and cisplatin, respectively, against the drug resistant MES-SA-DX5 uterine sarcoma cells. These p-coumarate esters were several times less effective against NIH/3T3 fibroblast cells. Docking studies showed that 1c may cause cytotoxicity by interaction with carbonic anhydrase IX. In conclusion, long chain alkyl esters of p-coumaric acid are promising scaffolds for selective apoptosis induction in cancer cells.
KW - apoptosis
KW - Cancer cell
KW - caspase-3
KW - cytotoxic activity
KW - hydroxycinnamic acids
UR - http://www.scopus.com/inward/record.url?scp=85028064983&partnerID=8YFLogxK
U2 - 10.1021/acs.jafc.7b01388
DO - 10.1021/acs.jafc.7b01388
M3 - Article
SN - 0021-8561
VL - 65
SP - 7228
EP - 7239
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
ER -