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Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy.
Cancer Lett. 2017 03 01; 388:292-302.CL

Abstract

Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. In vivo tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. In vivo pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy.

Authors+Show Affiliations

School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.Division of Nuclear Medicine, Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.Saha Institute of Nuclear Physics, Kolkata 700064, India.Division of Nuclear Medicine, Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India. Electronic address: mahitosh@smst.iitkgp.ernet.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28025102

Citation

Bharti, Rashmi, et al. "Somatostatin Receptor Targeted Liposomes With Diacerein Inhibit IL-6 for Breast Cancer Therapy." Cancer Letters, vol. 388, 2017, pp. 292-302.
Bharti R, Dey G, Banerjee I, et al. Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy. Cancer Lett. 2017;388:292-302.
Bharti, R., Dey, G., Banerjee, I., Dey, K. K., Parida, S., Kumar, B. N., Das, C. K., Pal, I., Mukherjee, M., Misra, M., Pradhan, A. K., Emdad, L., Das, S. K., Fisher, P. B., & Mandal, M. (2017). Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy. Cancer Letters, 388, 292-302. https://doi.org/10.1016/j.canlet.2016.12.021
Bharti R, et al. Somatostatin Receptor Targeted Liposomes With Diacerein Inhibit IL-6 for Breast Cancer Therapy. Cancer Lett. 2017 03 1;388:292-302. PubMed PMID: 28025102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy. AU - Bharti,Rashmi, AU - Dey,Goutam, AU - Banerjee,Indranil, AU - Dey,Kaushik Kumar, AU - Parida,Sheetal, AU - Kumar,B N Prashanth, AU - Das,Chandan Kanta, AU - Pal,Ipsita, AU - Mukherjee,Manabendra, AU - Misra,Mridula, AU - Pradhan,Anjan K, AU - Emdad,Luni, AU - Das,Swadesh K, AU - Fisher,Paul B, AU - Mandal,Mahitosh, Y1 - 2016/12/24/ PY - 2016/10/05/received PY - 2016/11/24/revised PY - 2016/12/16/accepted PY - 2016/12/28/pubmed PY - 2017/9/7/medline PY - 2016/12/28/entrez KW - Diacerein and breast cancer KW - Liposome KW - Somatostatin analogue (SST) SP - 292 EP - 302 JF - Cancer letters JO - Cancer Lett VL - 388 N2 - Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. In vivo tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. In vivo pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/28025102/Somatostatin_receptor_targeted_liposomes_with_Diacerein_inhibit_IL_6_for_breast_cancer_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(16)30784-4 DB - PRIME DP - Unbound Medicine ER -