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

Autor: Shah AM; Microbial Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India., Wani A; Cancer Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu Tawi, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India., Qazi PH; Microbial Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India. Electronic address: qphassan@iiim.ac.in., Rehman SU; Medicinal Chemistry Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India., Mushtaq S; Microbial Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India., Ali SA; Microbial Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India., Hussain A; Microbial Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India., Shah A; Microbial Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India., Qazi AK; Cancer Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu Tawi, India., Makhdoomi US; Cancer Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu Tawi, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India., Hamid A; Cancer Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu Tawi, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India., Kumar A; Cancer Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu Tawi, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180001, India.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2016 Aug 25; Vol. 256, pp. 198-208. Date of Electronic Publication: 2016 Jul 01.
DOI: 10.1016/j.cbi.2016.06.032
Abstrakt: 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.
(Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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