Tags

Type your tag names separated by a space and hit enter

Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy.
J Biol Regul Homeost Agents. 2010 Apr-Jun; 24(2):197-205.JB

Abstract

Multidrug resistance (MDR) in cancer cells is often caused by the high expression of the plasma membrane drug transporter P-glycoprotein (Pgp) associated with an elevated intracellular glutathione (GSH) content in various human tumors. Several chemosensitizers reverse MDR but have significant toxicities. Sedatives are often used to control anxiety and depression in cancer patients. In this in vitro study we investigated the effects of three plant derived sedatives such as apigenin (Api), fisetin (Fis), flavonoids and honokiol (Hnk) on Pgp activity and cellular GSH content in order to evaluate their potential use as chemosensitizing agents in anticancer chemotherapy. Human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp, were treated with each sedative alone (10 microM) or in combination with different doxo concentrations (2-8 microM). We measured the intracellular accumulation and cytotoxicity of doxo (MTT assay), the cellular GSH content (GSH assay) and ROS production (DFC-DA assay), in comparison with verapamil (Ver), a specific inhibitor for Pgp, used as reference molecule. We found that exposure at 2 and 8 microM doxo concentrations in the presence of Api, Fis and Hnk enhanced significantly doxo accumulation by 29+/-3.3, 20+/-4.8, 24+/-6.6 percent and 14+/-1.7, 8.3+/-4.2, 10.7+/-3.1 percent, respectively, when compared with doxo alone. These results were consistent with the increase of sensitivity towards doxo in MES-SA/Dx5, resulting in 1.7, 1.2, 1.4-fold and 1.2, 1.0 and 1.1-fold increases, respectively. Moreover, treatment with Api decreased markedly cellular GSH content (18 percent) and increased ROS production (greater than 20 percent) on MES-SA/Dx5 cells, while a significant reduction in ROS levels was observed in Hnk and Fis treated cells, when compared to untreated control. Our in vitro findings provide a rationale for innovative clinical trials to assess the use of natural sedatives or their derivatives as potential adjuvants to anticancer treatment for overcoming multidrug resistance Pgp-mediated in cancer patients.

Authors+Show Affiliations

Department of Medicine and Aging, School of Medicine and Aging Research Center, Ce.S.I. G. d'Annunzio University Foundation, Chieti-Pescara, Italy. aangelini@unich.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20487633

Citation

Angelini, Aantonio, et al. "Modulation of Multidrug Resistance P-glycoprotein Activity By Flavonoids and Honokiol in Human Doxorubicin- Resistant Sarcoma Cells (MES-SA/DX-5): Implications for Natural Sedatives as Chemosensitizing Agents in Cancer Therapy." Journal of Biological Regulators and Homeostatic Agents, vol. 24, no. 2, 2010, pp. 197-205.
Angelini A, Di Ilio C, Castellani ML, et al. Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. J Biol Regul Homeost Agents. 2010;24(2):197-205.
Angelini, A., Di Ilio, C., Castellani, M. L., Conti, P., & Cuccurullo, F. (2010). Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. Journal of Biological Regulators and Homeostatic Agents, 24(2), 197-205.
Angelini A, et al. Modulation of Multidrug Resistance P-glycoprotein Activity By Flavonoids and Honokiol in Human Doxorubicin- Resistant Sarcoma Cells (MES-SA/DX-5): Implications for Natural Sedatives as Chemosensitizing Agents in Cancer Therapy. J Biol Regul Homeost Agents. 2010 Apr-Jun;24(2):197-205. PubMed PMID: 20487633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. AU - Angelini,Aantonio, AU - Di Ilio,C, AU - Castellani,M L, AU - Conti,P, AU - Cuccurullo,F, PY - 2010/5/22/entrez PY - 2010/5/22/pubmed PY - 2010/8/21/medline SP - 197 EP - 205 JF - Journal of biological regulators and homeostatic agents JO - J Biol Regul Homeost Agents VL - 24 IS - 2 N2 - Multidrug resistance (MDR) in cancer cells is often caused by the high expression of the plasma membrane drug transporter P-glycoprotein (Pgp) associated with an elevated intracellular glutathione (GSH) content in various human tumors. Several chemosensitizers reverse MDR but have significant toxicities. Sedatives are often used to control anxiety and depression in cancer patients. In this in vitro study we investigated the effects of three plant derived sedatives such as apigenin (Api), fisetin (Fis), flavonoids and honokiol (Hnk) on Pgp activity and cellular GSH content in order to evaluate their potential use as chemosensitizing agents in anticancer chemotherapy. Human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp, were treated with each sedative alone (10 microM) or in combination with different doxo concentrations (2-8 microM). We measured the intracellular accumulation and cytotoxicity of doxo (MTT assay), the cellular GSH content (GSH assay) and ROS production (DFC-DA assay), in comparison with verapamil (Ver), a specific inhibitor for Pgp, used as reference molecule. We found that exposure at 2 and 8 microM doxo concentrations in the presence of Api, Fis and Hnk enhanced significantly doxo accumulation by 29+/-3.3, 20+/-4.8, 24+/-6.6 percent and 14+/-1.7, 8.3+/-4.2, 10.7+/-3.1 percent, respectively, when compared with doxo alone. These results were consistent with the increase of sensitivity towards doxo in MES-SA/Dx5, resulting in 1.7, 1.2, 1.4-fold and 1.2, 1.0 and 1.1-fold increases, respectively. Moreover, treatment with Api decreased markedly cellular GSH content (18 percent) and increased ROS production (greater than 20 percent) on MES-SA/Dx5 cells, while a significant reduction in ROS levels was observed in Hnk and Fis treated cells, when compared to untreated control. Our in vitro findings provide a rationale for innovative clinical trials to assess the use of natural sedatives or their derivatives as potential adjuvants to anticancer treatment for overcoming multidrug resistance Pgp-mediated in cancer patients. SN - 0393-974X UR - https://www.unboundmedicine.com/medline/citation/20487633/Modulation_of_multidrug_resistance_p_glycoprotein_activity_by_flavonoids_and_honokiol_in_human_doxorubicin__resistant_sarcoma_cells__MES_SA/DX_5_:_implications_for_natural_sedatives_as_chemosensitizing_agents_in_cancer_therapy_ L2 - https://medlineplus.gov/softtissuesarcoma.html DB - PRIME DP - Unbound Medicine ER -