Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)
Multidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as...
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MDPI AG
2019-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/10/512 |
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| author | Jessica Nayelli Sanchez-Carranza Leticia González-Maya Rodrigo Said Razo-Hernández Enrique Salas-Vidal Ninfa Yaret Nolasco-Quintana Aldo F. Clemente-Soto Lucero García-Arizmendi Mariana Sánchez-Ramos Silvia Marquina Laura Alvarez |
| author_facet | Jessica Nayelli Sanchez-Carranza Leticia González-Maya Rodrigo Said Razo-Hernández Enrique Salas-Vidal Ninfa Yaret Nolasco-Quintana Aldo F. Clemente-Soto Lucero García-Arizmendi Mariana Sánchez-Ramos Silvia Marquina Laura Alvarez |
| author_sort | Jessica Nayelli Sanchez-Carranza |
| collection | DOAJ |
| description | Multidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as they can reverse resistance to anticancer drugs and eventually resensitize cancer cells. We explore the chemosensitizing effect of Achillin, a guaianolide-type sesquiterpene lactone isolated from the Mexican medicinal plant <i>Artemisia ludovisiana</i>, to reverse MDR in Hep3B/PTX cells of hepatocellular carcinoma, which present resistance to paclitaxel (PTX). Achillin showed an important effect as chemosensitizer; indeed, the cytotoxic effect of PTX (25 nM) was enhanced, and the induction of G2/M phase cell cycle arrest and apoptosis were potentiated when combining with Achillin (100 μM). In addition, we observed that Achillin decreases P-gp levels and increases the intracellular retention of doxorubicin in Hep3B/PTX cells; in addition, homology structural modeling and molecular docking calculations predicted that Achillin interacts in two regions (M-site and R-site) of transporter drug efflux P-glycoprotein (P-gp). Our results suggest that the chemosensitizer effect demonstrated for Achillin could be associated with P-gp modulation. This work also provides useful information for the development of new therapeutic agents from guaianolide-type sesquiterpene lactones like Achillin. |
| first_indexed | 2024-04-14T02:26:35Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T02:26:35Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-82ceffc9034d465da36b789c5ddfa0de2022-12-22T02:17:51ZengMDPI AGPharmaceutics1999-49232019-10-01111051210.3390/pharmaceutics11100512pharmaceutics11100512Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)Jessica Nayelli Sanchez-Carranza0Leticia González-Maya1Rodrigo Said Razo-Hernández2Enrique Salas-Vidal3Ninfa Yaret Nolasco-Quintana4Aldo F. Clemente-Soto5Lucero García-Arizmendi6Mariana Sánchez-Ramos7Silvia Marquina8Laura Alvarez9Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoCentro de Investigación en Dinámica Celular-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoDepartamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca 62209, Morelos, MexicoCentro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoCentro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoCentro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoCentro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, MexicoMultidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as they can reverse resistance to anticancer drugs and eventually resensitize cancer cells. We explore the chemosensitizing effect of Achillin, a guaianolide-type sesquiterpene lactone isolated from the Mexican medicinal plant <i>Artemisia ludovisiana</i>, to reverse MDR in Hep3B/PTX cells of hepatocellular carcinoma, which present resistance to paclitaxel (PTX). Achillin showed an important effect as chemosensitizer; indeed, the cytotoxic effect of PTX (25 nM) was enhanced, and the induction of G2/M phase cell cycle arrest and apoptosis were potentiated when combining with Achillin (100 μM). In addition, we observed that Achillin decreases P-gp levels and increases the intracellular retention of doxorubicin in Hep3B/PTX cells; in addition, homology structural modeling and molecular docking calculations predicted that Achillin interacts in two regions (M-site and R-site) of transporter drug efflux P-glycoprotein (P-gp). Our results suggest that the chemosensitizer effect demonstrated for Achillin could be associated with P-gp modulation. This work also provides useful information for the development of new therapeutic agents from guaianolide-type sesquiterpene lactones like Achillin.https://www.mdpi.com/1999-4923/11/10/512achillinchemosensitizationmultidrug resistancepaclitaxelhepatocellular carcinomap-glycoprotein |
| spellingShingle | Jessica Nayelli Sanchez-Carranza Leticia González-Maya Rodrigo Said Razo-Hernández Enrique Salas-Vidal Ninfa Yaret Nolasco-Quintana Aldo F. Clemente-Soto Lucero García-Arizmendi Mariana Sánchez-Ramos Silvia Marquina Laura Alvarez Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX) Pharmaceutics achillin chemosensitization multidrug resistance paclitaxel hepatocellular carcinoma p-glycoprotein |
| title | Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX) |
| title_full | Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX) |
| title_fullStr | Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX) |
| title_full_unstemmed | Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX) |
| title_short | Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX) |
| title_sort | achillin increases chemosensitivity to paclitaxel overcoming resistance and enhancing apoptosis in human hepatocellular carcinoma cell line resistant to paclitaxel hep3b ptx |
| topic | achillin chemosensitization multidrug resistance paclitaxel hepatocellular carcinoma p-glycoprotein |
| url | https://www.mdpi.com/1999-4923/11/10/512 |
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