Abstract 5314: Evaluation of C-phycocyanin and anticancer drug combination for inducing apoptosis in LNCaP prostate cancer cells

Abstract

Abstract Natural products have been used for thousands of years by different culture and civilization to fight against diseases such as cancer. Modern medicine has begun to recognize the need to evaluate these natural products in terms of their potential therapeutic value with less toxic side effects. The discovery of novel natural anti-tumor compounds such as C-phycocyanin (C-PC) from the cyanobacterium Limnothrix sp., shows significant potential for inclusion in future drug regimens. C-PC is a pigment found in blue-green algae that have been proven to have antioxidant, anti-inflammatory and hepatoprotective properties. This cycanobacterium is relatively abundant in the estuaries and coastal waters of Florida's Everglades and the compound can be easily extracted from this natural resource. Mapping apoptosis mediated cancer cell death pathway can assist in paving way for the creation of future drug regimens with less toxic side effects in conjugation with a more potent therapeutic response. The main objective of our study was to evaluate apoptosis mediated cancer cell death against LNCaP prostate cancer cells using C-PC in combination with the well-known anti-cancer drug Topotecan (TPT). For this purpose several in vitro experiments were conducted in our laboratory to test whether lower than normal doses of the potent anticancer drug TPT can offer the same level of cytotoxicity as normal doses when combined with C-PC. Our experiments verified that when 10% of a typical dose of TPT was combined with C-PC, the cytotoxic effects towards LNCaP cancer cells were significantly higher than when TPT was used alone at its full dose. It is suspected that generation of ROS may play a crucial role in the overall process. However, the ultimate activation of key apoptotic proteases such as caspase-9 and caspase-3 appears to play a major part in the overall process. It was also observed that DNA fragmentation was more pronounced when both TPT and C-PC were used in combination for treatment. Furthermore, the expression level of the pro- and anti-apoptotic proteins such as Bcl-2 and Bax were also significantly modulated in cancer cells treated with C-PC and TPT combination. Higher levels of ROS generation as well as an increase in the activities of caspase-9 and caspase-3 detected in the combination treatments suggest that C-PC can augment apoptosis mediated cancer cell death and the therapeutic potentials of TPT. In that respect, we suggest that C-PC can improve the anticancer effects of several other anti-cancer drugs that are currently available and therefore could help to diminish many of the harsh side effects experienced by cancer patients undergoing chemotherapy. (This project was supported by the PFRDG grant of NSU and grants from the James & Esther King Biomedical Research Program of the State of Florida and The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida). Citation Format: Amal Khallouki, Hasan Azad, Sivanesan Dhandayuthapani, Miroslav Gantar, Appu Rathinavelu. Evaluation of C-phycocyanin and anticancer drug combination for inducing apoptosis in LNCaP prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5314. doi:10.1158/1538-7445.AM2015-5314