Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy

Rashmi Bharti, Goutam Dey, Indranil Banerjee, Kaushik Kumar Dey, Sheetal Parida, Prashanth Kumar Bhusetty Nagesh, Chandan Kanta Das, Ipsita Pal, Manabendra Mukherjee, Mridula Misra, Anjan K. Pradhan, Luni Emdad, Swadesh K. Das, Paul B. Fisher, Mahitosh Mandal

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalCancer Letters
Volume388
DOIs
StatePublished - Mar 1 2017

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diacetylrhein
Somatostatin Receptors
Liposomes
Interleukin-6
Breast Neoplasms
Somatostatin
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy. / Bharti, Rashmi; Dey, Goutam; Banerjee, Indranil; Dey, Kaushik Kumar; Parida, Sheetal; Bhusetty Nagesh, Prashanth Kumar; Das, Chandan Kanta; Pal, Ipsita; Mukherjee, Manabendra; Misra, Mridula; Pradhan, Anjan K.; Emdad, Luni; Das, Swadesh K.; Fisher, Paul B.; Mandal, Mahitosh.

In: Cancer Letters, Vol. 388, 01.03.2017, p. 292-302.

Research output: Contribution to journalArticle

Bharti, R, Dey, G, Banerjee, I, Dey, KK, Parida, S, Bhusetty Nagesh, PK, Das, CK, Pal, I, Mukherjee, M, Misra, M, Pradhan, AK, Emdad, L, Das, SK, Fisher, PB & Mandal, M 2017, 'Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy', Cancer Letters, vol. 388, pp. 292-302. https://doi.org/10.1016/j.canlet.2016.12.021
Bharti, Rashmi ; Dey, Goutam ; Banerjee, Indranil ; Dey, Kaushik Kumar ; Parida, Sheetal ; Bhusetty Nagesh, Prashanth Kumar ; Das, Chandan Kanta ; Pal, Ipsita ; Mukherjee, Manabendra ; Misra, Mridula ; Pradhan, Anjan K. ; Emdad, Luni ; Das, Swadesh K. ; Fisher, Paul B. ; Mandal, Mahitosh. / Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy. In: Cancer Letters. 2017 ; Vol. 388. pp. 292-302.
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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.",
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AU - Parida, Sheetal

AU - Bhusetty Nagesh, Prashanth Kumar

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

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