Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner via an immuno-modulatory circuit

BMC Complementary and Alternative Medicine

Research Article

Rathin Chakrabarty¹  Chinta Raveendar²  Anil Khurana²  Chaturbhuj Nayek²  Sanhita Mukherjee³  Gaurisankar Sa⁴  Uttam K Ghosh⁴  Shilpi Saha⁴  Dewan Md Sakib Hossain⁴  Minakshi Mazumdar⁴  Tanya Das⁴  Shravanti Mukherjee⁴  Suchismita Mohanty⁴ 

[1] Bholanath Chakrabarty Trust, 5, Subol Koley lane, 711101, Howrah, India;Central Council for Research in Homeopathy, 61-65, Institutional Area, 110058, Janakpuri, New Delhi, India;Department of Physiology, Calcutta National Medical College, 700014, Kolkata, India;Division of Molecular Medicine, Bose Institute, P1/12, 700054, CIT Scheme VIIM, Kolkata, India;

关键词: Apoptosis;    Cancer;    Calcarea carbonica;    Breast cancer;    p53;   

DOI  :  10.1186/1472-6882-13-230

 received in 2013-01-24, accepted in 2013-09-12,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundComplementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. However, the molecular mechanisms underneath the anti-cancer effect, if any, of these medicines have still remained unexplored. To this end we attempted to evaluate the efficacy of calcarea carbonica, a homeopathic medicine, as an anti-cancer agent and to delineate the detail molecular mechanism(s) underlying calcerea carbonica-induced tumor regression.MethodsTo investigate and delineate the underlying mechanisms of calcarea carbonica-induced tumor regression, Trypan blue dye-exclusion test, flow cytometric, Western blot and reverse transcriptase-PCR techniques were employed. Further, siRNA transfections and inhibitor studies were used to validate the involvement of p53 pathway in calcarea carbonica-induced apoptosis in cancer cells.ResultsInterestingly, although calcarea carbonica administration to Ehrlich’s ascites carcinoma (EAC)- and Sarcoma-180 (S-180)-bearing Swiss albino mice resulted in 30-35% tumor cell apoptosis, it failed to induce any significant cell death in ex vivo conditions. These results prompted us to examine whether calcarea carbonica employs the immuno-modulatory circuit in asserting its anti-tumor effects. Calcarea carbonica prevented tumor-induced loss of effector T cell repertoire, reversed type-2 cytokine bias and attenuated tumor-induced inhibition of T cell proliferation in tumor-bearing host. To confirm the role of immune system in calcarea carbonica-induced cancer cell death, a battery of cancer cells were co-cultured with calcarea carbonica-primed T cells. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells by calcarea carbonica i.e., (1) activation of the immune system of the host; and (2) induction of cancer cell apoptosis via immuno-modulatory circuit in p53-dependent manner by down-regulating Bcl-2:Bax ratio. Bax up-regulation resulted in mitochondrial transmembrane potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNA-interference inhibited calcarea carbonica-induced apoptosis thereby confirming the contribution of p53.ConclusionThese observations delineate the significance of immuno-modulatory circuit during calcarea carbonica-mediated tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea carbonica into immunotherapeutic strategies for effective tumor regression.

【 授权许可】

CC BY   
© Saha et al.; licensee BioMed Central Ltd. 2013