George SK, Radhakrishnan R, Sunil Kumar S, Sreelekha TT, Balaram P.
Integr Cancer Ther. 2013 Jun 7.
Regional Cancer Centre, Thiruvananthapuram, Kerala, India; Baylor College of Medicine, Houston, TX, USA.
Emerging trends for cancer chemotherapy show promising developments with the better understanding of molecules delivering more potent and powerful capabilities. But these are severely limited because of increased side effects and higher probability of tumor recurrence. In this scenario, putative exploration of the indigenous and untapped resources modulating immune system to deliver adequate but potent chemopreventive effects appeals considerable interest. However, these require rigorous scientific validation with regard to potency compared with the existing drugs. Aeglemarmelos (Linnaeus) Correa (family Rutaceae), a plant component of polyherbal formulation, Indukantha Ghritha, is known for its widespread medicinal values. But the chemopreventive potential has not been explored in comparison to existing anticancer agents. Our attempt contributes the scientific evidence for beneficial immunoprophylactic and antitumor functions in mice challenged with ascites tumors, Dalton’s lymphoma ascites, and Ehrlich’s ascites carcinoma either alone or in combination with cyclophosphamide and 5-fluorouracil. Specifically, the petroleum ether extracts of this plant (AMPE) prophylactically activated a cascade of host defense mechanisms by stimulating or restoring total white blood cell count, macrophage phagocytosis, hematopoiesis, lymphocyte proliferation and functions (CD4+ and CD8+) either naturally or under conditions of impaired immunity like in ascites tumor or during standard agent chemotherapy. Overall, AMPE also elicited strong antitumor effects by increasing median survival time and life span, while reducing murine ascites tumor volume and viable tumor counts on par with cyclophosphamide and 5-fluorouracil especially when administered prophylactically. This study also identified 2 putative components, xanthorrhizol and marmelosin, which could be imparting the immunoprophylactic and antitumor effects in transplantable tumor models. Thus, our attempts provide sufficient proof to warrant further to test this drug in higher animal models or in patients with high risk for tumor recurrence and/or immunocompromised diseases.