Noscapinoids bearing silver nanocrystals augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1, mouse melanoma skin cancer cells.

Abstract

PURPOSE:

Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1 mouse melanoma cancer cells.

METHODS AND RESULTS:

Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals were prepared separately by precipitation method. The mean particle size of Nos-Ag2+ nanocrystals was measured to be 25.33±3.52nm, insignificantly (P>0.05) different from 27.43±4.51nm of Red-Br-Nos-Ag2+ nanocrystals. Furthermore, zeta-potential of Nos-Ag2+ nanocrystals was determined to be -25.3±3.11mV significantly (P<0.05) different from -15.2±3.33mV of Red-Br-Nos-Ag2+ nanocrystals. The shape of tailored nanocrystals was slightly spherical and or irregular in shape. The architecture of Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals was crystalline in nature. FT-IR spectroscopy evinced the successful interaction of Ag2+ nanocrystals with Nos and Red-Br-Nos, respectively. The superior therapeutic efficacy of tailored nanocrystals was measured in terms of enhanced cytotoxicity, apoptosis and cellular uptake. The Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals exhibited an IC50 of 16.6μM and 6.5μM, significantly (P<0.05) lower than 38.5μM of Nos and 10.3μM of Red-Br-Nos, respectively. Finally, cellular morphological alterations in B16F1 cells upon internalization of Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals provided the evidences for accumulation within membrane-bound cytoplasmic vacuoles and in enlarged lysosomes and thus triggered mitochondria mediated apoptosis via caspase activation.

CONCLUSION:

Preliminary investigations substantiated that Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals must be further explored and utilized for the delivery of noscapinoids to melanoma cancer cells.

• Authors: Naina Soni, Kiran Jyoti, Upendra Kumar Jain, Anju Katyal, Ramesh Chandra, Jitender Madan
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 90 Pg. 906-913 (Jun 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28441716 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Silver
• Noscapine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems (methods)
• Humans
• Melanoma (drug therapy)
• Melanoma, Experimental (drug therapy)
• Mice
• Mitochondria (drug effects)
• Nanoparticles (chemistry)
• Noscapine (chemistry, pharmacology)
• Silver (chemistry)
• Skin Neoplasms (drug therapy)