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Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo.
Phytomedicine. 2014 Sep 25; 21(11):1221-9.P

Abstract

Our previous study has shown co-administration of guggulsterone resulted in significant increase in chemosensitivity of multidrug-resistant human breast cancer MCF-7/DOX cells to doxorubicin (DOX) in vitro. The present study was designed to investigate whether guggulsterone had the similar modulatory activities in vivo. MCF-7/DOX and MCF-7 xenograft mice models were established. At the end of the experiment (day 28), doxorubicin treatment alone did not significantly inhibit tumor growth in MCF-7/DOX xenograft, indicating that it retained doxorubicin resistance. Whereas, doxorubicin treatment alone significantly inhibited tumor growth in MCF-7 xenograft, suggesting that it maintained doxorubicin sensitivity. When doxorubicin and guggulsterone were co-administrated, their antitumor activities were augmented in MCF-7/DOX xenograft. However, combination therapy did not enhance the antitumor effects of doxorubicin in MCF-7 xenograft. The expression of proliferative cell nuclear antigens PCNA and Ki67 after doxorubicin treatment alone was not significantly different from that of vehicle group in MCF-7/DOX xenograft. On the contrary, doxorubicin treatment alone significantly reduced PCNA and Ki67 expression in MCF-7 xenograft. Combination therapy also significantly reduced PCNA and Ki67 expression in MCF-7/DOX xenograft, compared to doxorubicin treatment alone. However, combination therapy did not enhance the inhibitory effects of doxorubicin on PCNA and Ki67 expression in MCF-7 xenograft. Examining the apoptotic index by TUNEL assay showed similar results. Further studies demonstrated the inhibitory effects of guggulsterone on Bcl-2 and P-glycoprotein expression were the possible reason to increase chemosensitivity of MCF-7/DOX cells to doxorubicin in vivo. Examining body weight, hematological parameters, hepatic, cardiac and gastrointestinal tracts histopathology revealed that no significant signs of toxicity were related to guggulsterone. Guggulsterone might reverse doxorubicin resistance in vivo, with no severe side effects.

Authors+Show Affiliations

Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: xuhongbin@tongji.edu.cn.Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25172783

Citation

Xu, Hong-Bin, et al. "Reversal of Doxorubicin Resistance By Guggulsterone of Commiphora Mukul in Vivo." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 21, no. 11, 2014, pp. 1221-9.
Xu HB, Shen ZL, Fu J, et al. Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo. Phytomedicine. 2014;21(11):1221-9.
Xu, H. B., Shen, Z. L., Fu, J., & Xu, L. Z. (2014). Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 21(11), 1221-9. https://doi.org/10.1016/j.phymed.2014.06.003
Xu HB, et al. Reversal of Doxorubicin Resistance By Guggulsterone of Commiphora Mukul in Vivo. Phytomedicine. 2014 Sep 25;21(11):1221-9. PubMed PMID: 25172783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo. AU - Xu,Hong-Bin, AU - Shen,Zhao-Li, AU - Fu,Jin, AU - Xu,Lu-Zhong, Y1 - 2014/07/25/ PY - 2013/11/21/received PY - 2014/05/06/revised PY - 2014/06/09/accepted PY - 2014/8/31/entrez PY - 2014/8/31/pubmed PY - 2015/3/31/medline KW - Doxorubicin KW - Drug-resistance KW - Guggulsterone KW - Xenograft SP - 1221 EP - 9 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 21 IS - 11 N2 - Our previous study has shown co-administration of guggulsterone resulted in significant increase in chemosensitivity of multidrug-resistant human breast cancer MCF-7/DOX cells to doxorubicin (DOX) in vitro. The present study was designed to investigate whether guggulsterone had the similar modulatory activities in vivo. MCF-7/DOX and MCF-7 xenograft mice models were established. At the end of the experiment (day 28), doxorubicin treatment alone did not significantly inhibit tumor growth in MCF-7/DOX xenograft, indicating that it retained doxorubicin resistance. Whereas, doxorubicin treatment alone significantly inhibited tumor growth in MCF-7 xenograft, suggesting that it maintained doxorubicin sensitivity. When doxorubicin and guggulsterone were co-administrated, their antitumor activities were augmented in MCF-7/DOX xenograft. However, combination therapy did not enhance the antitumor effects of doxorubicin in MCF-7 xenograft. The expression of proliferative cell nuclear antigens PCNA and Ki67 after doxorubicin treatment alone was not significantly different from that of vehicle group in MCF-7/DOX xenograft. On the contrary, doxorubicin treatment alone significantly reduced PCNA and Ki67 expression in MCF-7 xenograft. Combination therapy also significantly reduced PCNA and Ki67 expression in MCF-7/DOX xenograft, compared to doxorubicin treatment alone. However, combination therapy did not enhance the inhibitory effects of doxorubicin on PCNA and Ki67 expression in MCF-7 xenograft. Examining the apoptotic index by TUNEL assay showed similar results. Further studies demonstrated the inhibitory effects of guggulsterone on Bcl-2 and P-glycoprotein expression were the possible reason to increase chemosensitivity of MCF-7/DOX cells to doxorubicin in vivo. Examining body weight, hematological parameters, hepatic, cardiac and gastrointestinal tracts histopathology revealed that no significant signs of toxicity were related to guggulsterone. Guggulsterone might reverse doxorubicin resistance in vivo, with no severe side effects. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/25172783/Reversal_of_doxorubicin_resistance_by_guggulsterone_of_Commiphora_mukul_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(14)00252-9 DB - PRIME DP - Unbound Medicine ER -