1. I am interested in the Summer Research Internship Program 2021 because it will give me
invaluable research experience and scientific knowledge from eminent scientific personnel
that will not only enhance my scientific potential but also instigate me to implement the
experience that will gain here in the near future as I pursue a career in M.Sc. Zoology. I also
believe that my curiosity and skills will be an asset to SRIP 2021 during my internship.
Cancer is the major cause of morbidity and mortality. The aforementioned topic entitled
“Development of small molecules for targeting mitochondria” will be highly beneficial to
understand the basic cross talk mechanism in cancer, which will be extremely beneficial to
develop and implement therapeutic regimen in cancer.
Conventional chemotherapy using Cytotoxic agents tends to damage both tumor and normal
cells and cause significant toxic side effects, which compromise the therapeutic outcomes.
Mitochondria structural and functional alterations associated with malignant transformation
seem to be a common phenomenon observed in many types of cancers. Utilizing these
differences to preferentially target mitochondria of cancer cells may be a logical strategy to
achieve therapeutic selectivity. Several classes of small molecules that directly target
mitochondria at specific sites or indirectly impact the metabolic alterations in cancer cells
with dysfunctional mitochondria seem to exhibit promising anticancer activity.
A novel class of triphenylphosphonium salts, TP compounds, with broad- spectrum
anticancer properties. TP421 exhibited sub-micromolar IC50 values in all the pancreatic
cancer cell lines tested using MTT and colony formation assays. TP421 localized
predominantly to mitochondria and induced G0/G1 arrest, ROS accumulation, and activation
of several stress-regulated kinases. Caspase and PARP-1 cleavage were observed indicating
an apoptotic response while LC3B-II and p62 were accumulated indicating inhibition of
autophagy. Furthermore, TP421 induced de-phosphorylation of key signaling molecules
involved in FAK mediated adhesion that correlated with inhibition of cell migration.
TP421 is a representative compound of a new promising class of mitochondrial-targeted
agents useful for pancreatic cancer treatment. Because of their unique mechanism of action
and efficacy further development is warranted.
SOP FOR A SUMMER INTERNSHIP