Dr. Weeks’ Comment: Now that more scientists are focusing on the real target to cure cancer – cancer STEM cells (CSC) and not cancer TUMOR cells (CTC), more oncologists are acknowledging the futility of conventional standards of care chemotherapy and radiation. Addressing cancer STEM cells is far more successful and less toxic than chemotherapy and radiation since the main intervention is anti-inflammation and powerful natural organic anti-inflammatory agents exist! So just Eat the seeds!
Anthothecol-encapsulated PLGA nanoparticles inhibit pancreatic cancer stem cell growth by modulating sonic hedgehog pathway
Authors: Raj Kumar Verma, Wei Yu, Surya Pratap Singh, Sharmila Shankar, Rakesh K. Srivastava
Published Online: July 19, 2015
DOI: http://dx.doi.org/10.1016/j.nano.2015.07.001
Abstract
Anthothecol, a limonoid derived from plant Khayaanthotheca (Meliaceae), is an antimalarial compound.
The objectives of this study were to examine the molecular mechanisms by which anthothecol-encapsulated PLGA-nanoparticles (Antho-NPs) regulate pancreatic cancer stem cell (CSC) characteristics and cell growth. Antho-NPs inhibited cell proliferation and colony formation, and induced apoptosis in pancreatic CSCs and cancer cell lines, but had no effects on HPNE cells.
Antho-NPs inhibited self-renewal capacity pancreatic CSCs isolated from human and KrasG12D mice.
Furthermore, antho-NPs suppressed cell motility, migration and invasion by up-regulating E-cadherin and inhibiting N-cadherin and Zeb1.
In addition, Antho-NPs inhibited pluripotency maintaining factors and stem cell markers, suggesting their inhibitory role on CSC population.
Anthothecol disrupted binding of Gli to DNA, and inhibited Gli transcription and Gli target genes. Our studies establish preclinical significance of Antho-NPs for the treatment and/or prevention of pancreatic cancer.