Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPARgamma in human colon cancer Caco-2 cells.
Bitter gourd (Momordica charantia) seed oil (BGO) is a unique oil which contains 9cis, 11trans, 13trans-conjugated linolenic acid (9c,11t,13t-CLN) at a high level of more than 60%. In this study, we investigated the anti-proliferative and apoptosis-inducing effects of free fatty acids prepared from BGO (BGO-FFA) using colon cancer Caco-2 cells. BGO-FFA and purified 9c,11t,13t-CLN remarkably reduced the cell viability of Caco-2. In Caco-2 cells treated with BGO-FFA, DNA fragmentation of apoptosis indicators was observed in a dose-dependent manner. The expression level of apoptosis suppressor Bcl-2 protein was also decreased by BGO-FFA treatment. The GADD45 and p53, which play an important role in apoptosis-inducing pathways, were remarkably up-regulated by BGO-FFA treatment in Caco-2 cells. Up-regulation of PPARgamma mRNA and protein were also observed during apoptosis induced by BGO-FFA. These results suggest that BGO-FFA rich in 9c,11t,13t-CLN may induce apoptosis in Caco-2 cells through up-regulation of GADD45, p53 and PPARgamma.
Yasui
Yumiko
Y
Graduate School of Fisheries Sciences, Hokkaido University, 3-1-1 Minato, Hakodate, Hokkaido 041-8611, Japan.
Hosokawa
Masashi
M
Sahara
Takehiko
T
Suzuki
Rikako
R
Ohgiya
Satoru
S
Kohno
Hiroyuki
H
Tanaka
Takuji
T
Miyashita
Kazuo
K
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008042:Linolenic Acids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D029777:Momordica charantia / Q000737:chemistry*; D047495:PPAR gamma / Q000235:genetics; D008517:Phytotherapy; D010938:Plant Oils / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation; D000097642:GADD45 Proteins
D000972:Antineoplastic Agents, Phytogenic; D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D008042:Linolenic Acids; D047495:PPAR gamma; D010938:Plant Oils; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins; C004934:eleostearic acid