Irradiation technology can improve the biological activities of natural molecules through a structural modification. This study was conducted to investigate the enhancement of the anticancer effects of chrysin upon exposure to gamma irradiation. Gamma irradiation induces the production of new radiolytic peaks simultaneously with the decrease of the chrysin peak, which increases the cytotoxicity in HT-29 human colon cancer cells. An isolated chrysin derivative (CM1) exhibited a stronger apoptotic effect in HT-29 cells than intact chrysin. The apoptotic characteristics induced by CM1 in HT-29 cells was mediated through the intrinsic signaling pathway, including the excessive production of included reactive oxygen species, the dissipation of the mitochondrial membrane potential, regulation of the B cell lymphoma-2 family, activation of caspase-9, 3, and cleavage of poly (adenosine diphosphate-ribose) polymerase. Our findings suggest that CM1 can be a potential anticancer candidate for the treatment of colon cancer.
Get full access to this article
View all access options for this article.
References
1.
RajKP, TaylorTH, WrayC, StamosMJ, ZellJA: Risk of second primary colorectal cancer among colorectal cancer cases: A population-based analysis. J Carcinog, 2011; 10:6.
2.
VolateSR, DavenportDM, MugaSJ, WargovichMJ: Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis, 2005; 26:1450–1456.
3.
AltmannKH, GertschJ: Anticancer drugs from nature—natural products as a unique source of new microtubule-stabilizing agents. Nat Prod Rep, 2007; 24:327–357.
4.
FanHC, ChiCS, ChangYK, TungMC, LinSZ, HarnHJ: The molecular mechanisms of plant-derived compounds targeting brain cancer. Int J Mol Sci, 2018; 19:E395.
5.
LuY, Zamora-RosR, ChanS, et al.: Dietary polyphenols in the aetiology of Crohn's disease and ulcerative colitis—A multicenter European Prospective Cohort Study (EPIC). Inflamm Bowel Dis, 2017; 23:2072–2082.
6.
EdmandsWM, FerrariP, RothwellJA, et al.: Polyphenol metabolome in human urine and its association with intake of polyphenol-rich foods across European countries. Am J Clin Nutr, 2015; 102:905–913.
7.
NagasakaM, HashimotoR, InoueY, et al.: Anti-tumorigenic activity of chrysin from Oroxylum indicum via non-genotoxic p53 activation through the ATM-Chk2 pathway. Molecules, 2018; 23:E1394.
8.
ZengYH, ZhouLY, ChenQZ, et al.: Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells. Oncol Rep, 2017; 38:456–464.
9.
IjazS, AkhtarN, KhanMS, et al.: Plant derived anticancer agents: A green approach towards skin cancers. Biomed Pharmacother, 2018; 103:1643–1651.
10.
MajeedT, WaniIA, HamdaniAM, BhatNA: Effect of sonication and gamma-irradiation on the properties of pea (Pisum sativum) and vetch (Vicia villosa) starches: A comparative study. Int J Biol Macromol, 2018; 114:1144–1150.
11.
JenjobA, UthairatanakijA, JitareeratP, Wongs-AreeC, Aiamla-OrS: Effect of harvest seasonal and gamma irradiation on the physicochemical changes in pineapple fruit cv. Pattavia during stimulated sea shipment. Food Sci Nutr, 2017; 5:997–1003.
12.
KangJA, SongHY, ByunEH, et al.: Gamma-irradiated black ginseng extract inhibits mast cell degranulation and suppresses atopic dermatitis-like skin lesions in mice. Food Chem Toxicol, 2018; 111:133–143.
13.
ByunEB, SungNY, KimJH, et al.: Enhancement of anti-tumor activity of gamma-irradiated silk fibroin via immunomodulatory effects. Chem Biol Interact, 2010; 186:90–95.
14.
BadaboinaS, BaiHW, NaYH, et al.: Novel radiolytic rotenone derivative, rotenoisin B with potent anti-carcinogenic activity in hepatic cancer cells. Int J Mol Sci, 2015; 16:16806–16815.
15.
ByunE-B, JangB-S, ByunE-H, SungN-Y: Effect of gamma irradiation on the change of solubility and anti-inflammation activity of chrysin in macrophage cells and LPS-injected endotoxemic mice. Radiat Phys Chem, 2016; 127:276–285.
16.
ByunEB, ParkSH, JangBS, SungNY, ByunEH: Gamma-irradiated beta-glucan induces immunomodulation and anticancer activity through MAPK and NF-kappaB pathways. J Sci Food Agric, 2016; 96:695–702.
17.
JeongGH, ChoJH, JoC, et al.: Gamma irradiation-assisted degradation of rosmarinic acid and evaluation of structures and anti-adipogenic properties. Food Chem, 2018; 258:181–188.
18.
ByunEB, SongHY, MushtaqS, et al.: Gamma-irradiated luteolin inhibits 3-isobutyl-1-methylxanthine-induced melanogenesis through the regulation of CREB/MITF, PI3K/Akt, and ERK pathways in B16BL6 melanoma cells. J Med Food, 2017; 20:812–819.
19.
ZhangJ, WangX, VikashV, et al.: ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev, 2016; 2016:4350965.
20.
YangG, BaiY, WuX, et al.: Patulin induced ROS-dependent autophagic cell death in human hepatoma G2 cells. Chem Biol Interact, 2018; 288:24–31.
21.
ShimizuS, NaritaM, TsujimotoY: Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature, 1999; 399:483–487.
22.
KimR: Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer, 2005; 103:1551–1560.
23.
BinQ, RaoH, HuJN, et al.: The caspase pathway of linoelaidic acid (9t, 12t-c18:2)-induced apoptosis in human umbilical vein endothelial cells. Lipids, 2013; 48:115–126.
24.
PistrittoG, TrisciuoglioD, CeciC, GarufiA, D'OraziG: Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging, 2016; 8:603–619.
25.
BhatiaM: Apoptosis versus necrosis in acute pancreatitis. Am J Physiol Gastrointest Liver Physiol, 2004; 286:G189–G196.
VallejoMJ, SalazarL, GrijalvaM: Oxidative stress modulation and ROS-mediated toxicity in cancer: A review on in vitro models for plant-derived compounds. Oxid Med Cell Longev, 2017; 2017:4586068.
28.
CzabotarPE, LesseneG, StrasserA, AdamsJM: Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nat Rev Mol Cell Biol, 2014; 15:49–63.
29.
FarahM, ParharK, MoussaviM, EivemarkS, SalhB: 5,6-Dichloro-ribifuranosylbenzimidazole- and apigenin-induced sensitization of colon cancer cells to TNF-alpha-mediated apoptosis. Am J Physiol Gastrointest Liver Physiol, 2003; 285:G919–G928.
30.
BrentnallM, Rodriguez-MenocalL, De GuevaraRL, CeperoE, BoiseLH: Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol, 2013; 14:32.
31.
PutinskiC, Abdul-GhaniM, StilesR, et al.: Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy. Proc Natl Acad Sci USA, 2013; 110:E4079–E4087.
32.
SubasicD, StoegerT, EisenringS, et al.: Post-transcriptional control of executioner caspases by RNA-binding proteins. Genes Dev, 2016; 30:2213–2225.
33.
HuppertzB, FrankHG, KaufmannP: The apoptosis cascade—morphological and immunohistochemical methods for its visualization. Anat Embryol (Berl), 1999; 200:1–18.
34.
VelezC, ZayasB, KumarA: Biological activity of N-hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin derivatives upon colorectal adenocarcinoma cells. Open J Med Chem, 2014; 4:1–11.
35.
KrezelI: New derivatives of imidazole as potential anticancer agents. Farmaco, 1998; 53:342–345.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
