am6b13352_si_001.pdf (2.51 MB)
Cancer Cell Specific Delivery of Photosystem I Through Integrin Targeted Liposome Shows Significant Anticancer Activity
journal contribution
posted on 2016-12-06, 00:00 authored by Abhijit Saha, Saswat Mohapatra, Gaurav Das, Batakrishna Jana, Subhajit Ghosh, Debmalya Bhunia, Surajit GhoshMany
anticancer drugs are developed for the treatment of cancer from natural
sources. Photosystem I (PSI), a protein complex present in the chloroplast,
is involved in photosynthesis and generates reactive oxygen species
(ROS) in plant. Here, we used the ROS generation property of PSI for
cancer therapy. We show that PSI can enter into different kinds of
cancer cell like human lung carcinoma (A549) and mouse melanoma (B16F10)
cell lines and generate ROS inside the cells. It inhibits the proliferation
of cancer cell and causes apoptotic death of cancer cells. We also
show that PSI induces apoptosis through mitochondria-dependent internal
pathway, induces caspase3, causes DNA fragmentation, and arrests cell
cycle at SubG0 phase. We also prepared, using C16-LDV lipopeptide
[C16 long chain attached on the N-terminal of the tripeptide containing
amino acids leucine (L), aspartic acid (D), and valine (V) abbreviated
as NH2-LDV-COOH], α4β1 integrin targeted liposomal formulation of PSI, which specifically
kills the cancer cell without affecting normal cells, and it is found
to be more potent compared to clinically used drug doxorubicin. Finally,
we found that LDV liposomal formulation of PSI inhibits the growth
of tumor in C57BL/6J mice model.