Inhibitory effect of quercetin on colorectal lung metastasis through inducing apoptosis, and suppression of metastatic ability.
BACKGROUND
Quercetin is a major dietary flavonoid found in a various fruits, vegetables, and grains. Although the inhibitory effects of quercetin have previously been observed in several types of cancer cells, the anti-metastatic effect of quercetin on colorectal metastasis has not been determined.


OBJECTIVE
This study investigated whether quercetin exhibits inhibitory effect on colorectal lung metastasis.


METHODS
The effects of quercetin on cell viability, mitogen-activated protein kinases (MAPKs) activation, migration, invasion, epithelial-mesenchymal transition (EMT) and lung metastasis were investigated.


METHODS
We investigated the effect of quercetin on metastatic colon cancer cells using WST assay, Annexin V assay, real-time RT-PCR, western blot analysis and gelatin zymography. The anti-metastatic effect of quercetin in vivo was confirmed in a colorectal lung metastasis model.


RESULTS
Quercetin inhibited the cell viability of colon 26 (CT26) and colon 38 (MC38) cells and induced apoptosis through the MAPKs pathway in CT26 cells. Expression of EMT markers, such as E-, N-cadherin, β-catenin, and snail, were regulated by non-toxic concentrations of quercetin. Moreover, the migration and invasion abilities of CT26 cells were inhibited by quercetin through expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulation. Quercetin markedly decreased lung metastasis of CT26 cells in an experimental in vivo metastasis model.


CONCLUSIONS
In conclusion, this study demonstrates for the first time that quercetin can inhibit the survival and metastatic ability of CT26 cells, and it can subsequently suppress colorectal lung metastasis in the mouse model. These results indicate that quercetin may be a potent therapeutic agent for the treatment of metastatic colorectal cancer.
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.
Ji-Ye
JY
Kee
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.
Yo-Han
YH
Han
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.
Dae-Seung
DS
Kim
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.
Jeong-Geon
JG
Mun
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Jinbong
J
Park
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea; Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Mi-Young
MY
Jeong
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: jyum@khu.ac.kr.
Jae-Young
JY
Um
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea. Electronic address: jooklim@wonkwang.ac.kr.
Seung-Heon
SH
Hong
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D011794:Quercetin; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases
Apoptosis; Colorectal cancer; Lung metastasis; Mitogen-activated protein kinases; Quercetin