Homeopathic mother tincture of Phytolacca decandra induces apoptosis in skin melanoma cells by activating caspase-mediated signaling via reactive oxygen species elevation

• Published in: Journal of integrative medicine Vol. 11; no. 2; pp. 116 - 124
• Main Authors: Ghosh, Samrat, Bishayee, Kausik, Paul, Avijit, Mukherjee, Avinaba, Sikdar, Sourav, Chakraborty, Debrup, Boujedaini, Naoual, Khuda-Bukhsh, Anisur Rahman
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2013
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; apoptosis; Apoptosis - drug effects; Caspase 3 - genetics; Caspase 3 - metabolism; Cell Line, Tumor; Drugs, Chinese Herbal - pharmacology; gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; Melanoma - drug therapy; Melanoma - genetics; Melanoma - metabolism; Melanoma - physiopathology; Phytolacca - chemistry; Phytolacca decandra; Phytotherapy; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; skin neoplasms; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - physiopathology; Up-Regulation - drug effects; 介导; 信号; 半胱天冬酶; 活性氧; 激活; 皮肤疾病; 细胞凋亡; 黑色素瘤; apoptosis; skin neoplasms; Phytolacca decandra; gene expression; reactive oxygen species
• ISSN: 2095-4964
• DOI: 10.3736/jintegrmed2013014

OBJECTIVE： Preventive measures against skin melanoma like chemotherapy are useful but suffer from chronic side effects and drug resistance. Ethanolic extract of Phytolacca decandra （PD）, used in homeopathy for the treatment of various ailments like chronic rheumatism, regular conjunctivitis, psoriasis, and in some skin diseases was tested for its possible anticancer potential. METHODS： Cytotoxicity of the drug was tested by conducting 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide assay on both normal （peripheral blood mononuclear cells） and A375 cells. Fluorescence microscopic study of 4＇,6-diamidino-2-phenylindole dihydrochloride-stained cells was conducted for DNA fragmentation assay, and changes in cellular morphology, if any, were also recorded. Lactate dehydrogenase activity assay was done to evaluate the percentages of apoptosis and necrosis. Reactive oxygen species （ROS） accumulation, if any, and expression study of apoptotic genes also were evaluated to pin-point the actual events of apoptosis. RESULTS： Results showed that PD administration caused a remarkable reduction in proliferation of A375 cells, without showing much cytotoxicity on peripheral blood mononuclear cells. Generation of ROS and DNA damage, which made the cancer cells prone to apoptosis, were found to be enhanced in PD-treated cells. These results were duly supported by the analytical data on expression of different cellular and nuclear proteins, as for example, by down- regulation of Akt and Bcl-2, up-regulation of p53, Bax and caspase 3, and an increase in number of cell deaths by apoptosis in A375 cells. CONCLUSION： Overall results demonstrate anticancer potentials of PD on A375 cells through activation of caspase-mediated signaling and ROS generation.