Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest
Colorectal cancer (CRC) is one of the diseases with the highest rates of prevalence and mortality despite therapeutic methods in the world. In particular, there are not enough methods to treat metastasis of CRC cells to distant organs. <i>Cannabis sativa</i> Linne (<i>C. sativa<...
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2022-10-01
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author | Jeong-Geon Mun Hee Dong Jeon Dae Hwan Yoon Yoon Seung Lee Shin Young Park Jong-Sik Jin Noh-Joon Park Ji-Ye Kee |
author_facet | Jeong-Geon Mun Hee Dong Jeon Dae Hwan Yoon Yoon Seung Lee Shin Young Park Jong-Sik Jin Noh-Joon Park Ji-Ye Kee |
author_sort | Jeong-Geon Mun |
collection | DOAJ |
description | Colorectal cancer (CRC) is one of the diseases with the highest rates of prevalence and mortality despite therapeutic methods in the world. In particular, there are not enough methods to treat metastasis of CRC cells to distant organs. <i>Cannabis sativa</i> Linne (<i>C. sativa</i>) is a popular medicinal plant used by humans to treat many diseases. Recently, extracts of <i>C. sativa</i> have shown diverse pharmacological effects as a result of choosing different extraction methods. In this study, we performed experiments to confirm the inhibitory effect and related mechanisms of supercritical extract of <i>C. sativa</i> on metastatic CRC cells. The effect of SEC on the viability of CRC cell lines, CT26 and HCT116, was determined using CCK reagent. Flow cytometry was performed to confirm whether SEC can promote cell cycle arrest and apoptosis. Additionally, SEC reduced proliferation of CT26 and HCT116 cells without causing toxicity to normal colon cell line CCD-18Co cells. SEC treatment reduced colony formation in both CRC cell lines, promoted G0/G1 phase arrest and apoptosis in CT26 and HCT116 cells through AMPK activation and MAPKs such as ERK, JNK, and p38 inactivation. Moreover, oral administration of SEC decreased pulmonary metastasis of CT26 cells. Our research demonstrates the inhibitory effect of SEC on CRC cell proliferation and metastasis. Thus, SEC might have therapeutic potential for CRC treatment. |
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spelling | doaj.art-c9a3c738139c47f7ab829215831c942e2023-11-24T06:13:23ZengMDPI AGNutrients2072-66432022-10-011421454810.3390/nu14214548Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle ArrestJeong-Geon Mun0Hee Dong Jeon1Dae Hwan Yoon2Yoon Seung Lee3Shin Young Park4Jong-Sik Jin5Noh-Joon Park6Ji-Ye Kee7Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, KoreaDepartment of Oriental Medicine Resources, Jeonbuk National University, 79 Gobong-ro, Iksan 54596, Jeonbuk, KoreaSemi Led Co., Ltd., 109 Ballyong-ro, Deokjin-gu, Jeonju-si 54853, Jeollabuk-do, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, KoreaColorectal cancer (CRC) is one of the diseases with the highest rates of prevalence and mortality despite therapeutic methods in the world. In particular, there are not enough methods to treat metastasis of CRC cells to distant organs. <i>Cannabis sativa</i> Linne (<i>C. sativa</i>) is a popular medicinal plant used by humans to treat many diseases. Recently, extracts of <i>C. sativa</i> have shown diverse pharmacological effects as a result of choosing different extraction methods. In this study, we performed experiments to confirm the inhibitory effect and related mechanisms of supercritical extract of <i>C. sativa</i> on metastatic CRC cells. The effect of SEC on the viability of CRC cell lines, CT26 and HCT116, was determined using CCK reagent. Flow cytometry was performed to confirm whether SEC can promote cell cycle arrest and apoptosis. Additionally, SEC reduced proliferation of CT26 and HCT116 cells without causing toxicity to normal colon cell line CCD-18Co cells. SEC treatment reduced colony formation in both CRC cell lines, promoted G0/G1 phase arrest and apoptosis in CT26 and HCT116 cells through AMPK activation and MAPKs such as ERK, JNK, and p38 inactivation. Moreover, oral administration of SEC decreased pulmonary metastasis of CT26 cells. Our research demonstrates the inhibitory effect of SEC on CRC cell proliferation and metastasis. Thus, SEC might have therapeutic potential for CRC treatment.https://www.mdpi.com/2072-6643/14/21/4548<i>Cannabis sativa</i>colorectal cancerapoptosiscell cycle arrestMAPKsAMPK |
spellingShingle | Jeong-Geon Mun Hee Dong Jeon Dae Hwan Yoon Yoon Seung Lee Shin Young Park Jong-Sik Jin Noh-Joon Park Ji-Ye Kee Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest Nutrients <i>Cannabis sativa</i> colorectal cancer apoptosis cell cycle arrest MAPKs AMPK |
title | Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest |
title_full | Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest |
title_fullStr | Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest |
title_full_unstemmed | Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest |
title_short | Supercritical Extract of <i>Cannabis sativa</i> Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest |
title_sort | supercritical extract of i cannabis sativa i inhibits lung metastasis in colorectal cancer cells by increasing ampk and mapks mediated apoptosis and cell cycle arrest |
topic | <i>Cannabis sativa</i> colorectal cancer apoptosis cell cycle arrest MAPKs AMPK |
url | https://www.mdpi.com/2072-6643/14/21/4548 |
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