Isolation and characterization of alborixin from Streptomyces scabrisporus: A potent cytotoxic agent against human colon (HCT-116) cancer cells

• Published in: Chemico-biological interactions 2016-08, Vol.256, p.198-208
• Main Authors: Shah, Aabid Manzoor, Wani, Abubakar, Qazi, Parvaiz H., Rehman, Shakeel-u, Mushtaq, Saleem, Ali, Shiekh Abid, Hussain, Aehtesham, Shah, Aiyatullah, Qazi, Asif Khurshid, Makhdoomi, Ubaid Sharif, Hamid, Abid, Kumar, Ajay
• Format: Article
• Language: English
• Subjects: Alborixin; Anticancer; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Colon - drug effects; Colon - metabolism; Colon - pathology; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; HCT-116; HCT116 Cells; Humans; Kashmir Himalayas; Membrane Potential, Mitochondrial - drug effects; Pyrans - chemistry; Pyrans - isolation & purification; Pyrans - pharmacology; Reactive Oxygen Species - metabolism; Streptomyces - chemistry; Streptomyces scabrisporus
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2016.06.032

The ethyl acetate extract from the fermentation broth of an actinomycete strain, identified as Streptomyces scabrisporus isolated from soil of Kashmir Himalayas – India, exhibited significant cytotoxic activity against a panel of human cancer cell lines. The active fraction subjected to column chromatography led to the isolation of pharmacologically potent anticancer compound whose structure was established to be alborixin on the basis of spectral data analysis. The compound exhibited antiproliferative activity against panel of cell lines N2a, MCF-7, MiaPaca-2, PC-3, HCT-116, MDA-MB-231, HL-60 and A-549 cells with IC50 of 9.7, 15.4, 7.2, 8.1, 3.2, 9.7, 7.5 and 11.5 μM respectively. Alborixin displayed the maximum cytotoxic activity against HCT-116 human colon carcinoma cells and therefore further studies were carried on this cell line. Alborixin decreased the clonogenic potential of HCT-116 cells in a dose dependent manner. It induced apoptotic cell death in HCT116 cells that were confirmed by Flow cytometric analysis of Annexin V/PI staining and microscopic examination of cellular morphology through DAPI-stained cells. Biochemical evidence of apoptosis came from elevating the intracellular ROS level that was accompanied by mitochondrial membrane potential loss, decreasing the expression profile of anti-apoptotic protein Bcl-2, whereas it augments cleavage of caspase-3 and PARP-1, activates caspase-8 and 9 with concomitant increase in expression of proapoptotic protein Bax in a dose dependent manner. These results indicate that alborixin obtained from Streptomyces scabrisporus IIIM55 induces apoptotic cell death in colon cancer cells HCT-116 and can be further evaluated for its potential as an anticancer agent. •Isolation of actinomycetes from soil samples collected from Kashmir Himalayas.•Screening of actinomycetes for cytotoxic activity.•Identification and phylogenetic analysis of potent Strain (IIIM55).•Isolation and structure elucidation of the bioactive compound from the Streptomyces scabrisporus (IIIM55).•Assessment of anti-cancerous activity of purified compound (alborixin).