New anti-cancer agent, highly potent against chemo-resistant cancer has been characterized

1. New anti-cancer agent, highly potent against chemo-resistant cancer has been characterized Development of drug resistance is a major obstacle against successful chemotherapy of many currently-used anticancer drugs in clinics as the resistance often leads to recurrence of the disease. CIL-102, a plant (Zanthoxylumsimulans) derived alkaloid is highly potent against multi-drug resistant cancer. We have identified the cellular target of CIL-102 and unraveled the mechanisms of action of the drug in breast cancer cells. Our findings suggest that CIL-102 may be considered as a potential lead compound in anticancer therapy, especially against chemo-resistant cancer. KK Gireesh, Rashid A, Chakraborty S, Panda D, and Manna T* Biochemical Pharmacology (in Press)

2. CIL-102 binds to microtubule protein tubulin at a novel site. Molecular modeling Binding analysis by Isothermal titration calorimetry (ITC)

3. CIL-102 induces severe phenotypes like, monopolarity and multinucleation in breast cancer cells

4. CIL-102 kills cancer cells via p53-p21 pathway Annexin V

5. Other on-going projects in the lab Understanding the functional and molecular basis of end binding (EB) proteins in microtubule regulation, chromosome segregation, cell polarity and tumorigenesis. End binding (EB) proteins localize to growing end tips of microtubule cytoskeleton. They track plus end tips and mediate the interactions of microtubules with other cellular components, including chromosomes, cell cortex etc. They are implicated in cell division, maintenance of cell polarity and growth. Some of them, such as EB1 has been strongly linked to tumorigenesis. It is highly expressed in cancer and stimulates cancer growth. We are interested to understand the molecular basis of its tumorigenic role, and the mechanisms by which EBs regulate microtubule cytoskeleton, chromosome segregation and cell polarity in mammalian cells.

6. Understanding the pathways of Centrosome and centriole biogenesis, molecular and structural basis of centrosome mediated microtubule regulation, cellular asymmetry and cell polarity in mammalian cells Centrosome is a subcellular organelle involved in a vast majority of microtubule regulation and organization processes. It is involved in cell division, cell migration and cell polarity. It consists of two centrioles which give birth of two daughter centrioles, the process which duplicates centrosome into two during cell cycle. Centrosome duplication occurs once per cell cycle and needs to precede precisely in accordance with nuclear division. Deregulation of centrosome/centriole biogenesis pathway gives rise to cells with extra centrosome (supernumerary), fragmented immature centrosomal components which cause severe cell division defects, aneuploidy/polyploidy and genetic instability. Supernumerary and fragmented centrosomes are common hallmarks of cancer. Centrosomal abnormalities are also thought to be associated with many developmental disorders. Our long term goal is to understand the molecular basis of centrosome/centriole biogenesis and centrosome mediated cellular processes.