Ramesh C. Gupta, PhD

Ramesh C. Gupta, PhD

Dr. Ramesh C. Gupta received PhD in Chemistry from the Roorkee University (now Indian Institute of Technology), India, and then moved to Baylor College of Medicine, Houston for postdoctoral training in 1973. He grew to Associate Professor at Baylor prior to moving to University of Kentucky in 1989 as Professor. In 2003, he was recruited by James Graham Brown Cancer Center, University of Louisville and was appointed as Professor, Distinguished University Scholar and Agnes Brown Duggan Chair in Oncological Research. He has always worked at the cutting edge technology pioneering sensitive methods to sequence tRNAs, followed by ultrasensitive 32P-postlabeling to measure DNA damage by environmental carcinogens. These works have received several thousand citations.

Last year, Dr. Gupta’s laboratory reported the development of novel polymeric implants for continuously (“24/7”) delivering natural compounds for long duration for prevention and treatment of cancer. This technology has been filed for patents by the University of Louisville – part of the patent issued in March 2012. His recent focus has been to identify natural compounds and extracts which attack multiple targets for preventing lung, breast and cervical cancers. His laboratory was the first to report the inhibition of breast cancer and lung cancer by blueberry ‘colored’ compounds, and cervical cancer by withaferin A isolated from the ancient Indian herb “ashwagandha”. The blueberry compounds have also elicited enhanced response of chemotherapeutic drugs which led to a lung cancer clinical trial.

The laboratory’s thrust is to develop simple and effective strategies for prevention and treatment of cancer recurrence and metastasis using blueberry bioactives and other natural compounds and novel drug delivery systems. He has been fortunate to have a qualified team of researchers, continuous funding from NIH and State grants, the Duggan endowment and James Graham Brown Cancer Center.

Abstract

Therapeutic Potential of Blueberry Anthos (‘Colored’ Therapy)

Ramesh Gupta, Farrukh Aqil, Hina Kausar, Jeyaprakash Jeyabalan,
Manicka Vadhanam and Radha Munagala, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky

Early detection and discovery of new targeted drugs has resulted in increased survival for patients with several cancer types. However, no significant progress has been made for lung cancer and pancreatic cancer where the 5-year survival still hovers around 15% and 5%, respectively. Furthermore, there are essentially no cancer management strategies to delay or prevent the recurrence and metastasis of the disease. It is highly timely that unconventional and user-friendly alternate approaches be developed. What is needed is a multi-pronged approach in which non-toxic natural compounds attack distinct molecular targets associated with the tumor growth, and keep the disease progression halted, if not cure it. Colored pigments present particularly in berries are gaining high visibility for their chemopreventive and chemotherapeutic potential. Several papers published from this laboratory have shown significant chemopreventive and chemotherapeutic activities of colored pigments and other polyphenolics in blueberry and black raspberry1-5. Our more recent data reveal potent therapeutic activity of anthocyanidins (Anthos) from blueberry (Figure) against lung, breast, and pancreatic cancers in cell culture.

In fact, the data revealed that blueberry Anthos act in concert to produce synergistic effects. This synergism presumably resulted from attack of the individual Anthos on distinct and overlapping molecular targets associated with cell proliferation, apoptosis, inflammation and invasion. Detection of all the five Anthos present in blueberry in the lung tissue of mice and rats dosed with either dietary blueberry or isolated Anthos by HPLC and LC-MS/MS combined with their chemopreventive/chemotherapeutic activities against breast cancer and lung cancer in vivo clearly indicate that these compounds elicit response beyond the GI tract. Furthermore, blueberry Anthos when combined with standard chemotherapeutic (chemo) drugs produced enhanced response of the drug against lung cancer cells both in cell culture and nude mouse xenograft model. The enhanced response of blueberry Anthos was also observed in conjunction with gemcitabin against pancreatic cancer cells, with paclitaxel and doxorubicin against both ER-positive and triple-negative breast cancer cells. The data discussed here suggest that blueberry Anthos can be developed as a potent therapeutic drug per se to kill a variety of human cancer cells, as well as enhance the therapeutic response of chemo drugs. (Work supported by USPHS grants CA118114 and CA-125152, Kentucky Lung Cancer Research Program, Agnes Brown Duggan Endowment, and Helmsley Trust Funds).

References
Aiyer, H.S., Srinivasan, C., Gupta, R.C. Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in
ACI rats. Nutr Cancer. 60(2):227-34, 2008.
Aiyer HS, Gupta RC. Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of
estrogen metabolism. Cancer Prev Res (Phila). 3(6):727-37, 2010.
Vadhanam, M.V., Ravoori, S., Aqil, F., and Gupta, R.C. Chemoprevention of mammary carcinogenesis by sustained systemic
delivery of ellagic acid. European Journal of Cancer Prevention. 20: 484-891, 2011.
Ravoori, S., Vadhanam, M.V., Aqil, F. and Gupta R.C. Inhibition of estrogen-mediated mammary tumorigenesis by blueberry and
black raspberry. Journal of Agricultural and Food Chemistry, 60: 5547-55, 2012.
Kausar, H., Jeyabalan, J., Aqil, F., Chabba, D., Sidana, J., Singh, I.P. and Gupta, R.C. Berry anthocyanidins synergistically
suppresses growth and metastatic potential of human non-small-cell lung cancer cells. Cancer Letters, 325: 54-62, 2012.