Abstract
The present study was an effort to establish the anticancer activity of the purified protein toxin (drCT-II) from Indian Russell’s viper (Daboia russelli russelli) venom in leukemic cell line and animal model. Isolation and purification of drCT-II was done through CM-cellulose ion exchange chromatography and RP- HPLC. SDS- PAGE molecular weight and first 20 amino acid sequence of drCT-II was done. The anti-leukemic activity using U937 and K562 cell line was established through cytotoxicity, apoptosis, cell cycle study, morphology, cancer marker proteins. The mean survival time of EAC induced male albino mice was established. Human lymphocyte cytotoxicity was done. drCT-II was eluted with 0.1 M NaCl on CM-cellulose ion exchange chromatography. On RP-HPLC, drCT-II produced single peak with retention time of 14.6 min. SDS-PAGE molecular weight was found to be 6.6 KDa and the first 20 amino acid sequence was found to be LQXNKLVPIASKTXPPGKNL. drCT-II produced time and dose dependent cell (U937 and K562) growth inhibition. The IC50 was found to be 35.5 μg/ml for U937 cell and 48.2 μg/ml for K562 cells. drCT-II produced membrane disruption, blebbing and nuclear disintegration in U937 and K562 cells observed through confocal and scanning electron microscopy. It exhibited DNA fragmentation and comet formation in leukemic cells. drCT-II produced apoptosis, cell cycle arrest at G1 phase and increased the expression of P21, P27 and P53. drCT-II induced apoptosis in leukemic cells was followed through caspase 3 and 9 pathway activation. EAC cell growth in male albino mice was significantly inhibited by drCT-II, thus increased the mean survival time. drCT-II significantly reduced the human lymphocyte count (in culture). It may be concluded that drCT-II, a 6.6 KDa protein purified from Daboia russelli russelli venom would be a novel pro-apoptotic agent that induced cancer cell killing through p53 and caspase pathway.
Highlights
Cancer, one of the largest killer diseases contributed a projected death toll of more than eight million lives per year, across the globe [1]
The purified fraction constitutes about 2.75 ± 0.05% protein of the venom applied onto the column
DrCT-II a protein (6.6 KDa) toxin was isolated from Indian Daboia russelli russelli venom which showed significant cytotoxic activity on leukemic cell lines and Ehrlich ascites carcinoma (EAC) bearing mice
Summary
One of the largest killer diseases contributed a projected death toll of more than eight million lives per year, across the globe [1]. It remained as the second most deadly disease over the last millennium but expected to surpass heart disease early in the present century [2]. In India, improved nutrition, mass awareness, modernization of sanitation and availability of advanced diagnostic and therapeutic option enabled an overall decline in mortality and morbidity from other class of diseases. The therapeutic and epidemiological perspectives have spurred the quest for newer diagnostic and treatment options towards cancer treatment and prevention. The application of current treatment technique, which includes surgical, radiation therapy, chemotherapy, biological therapy, results in the cure / remission in only half of these patients [5]
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