NOVEL COLCHICINE ANALOGUES TARGET MITOCHONDRIAL PT PORES USING FREE TUBULINS AND INDUCE ROS-MEDIATED APOPTOSIS IN CANCEROUS LYMPHOCYTES

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AGHVAMI MARJAN; ESHGHI PEYMAN; Zarei Mohammad Hadi; AREFI HADI; SATTARI FATEMEH; ZARGHI AFSHIN; POURAHMAD JALAL

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Journal: Iranian Journal of Pharmaceutical Research Year:2018 | Volume:17 | Issue:4 Page(s): 1476-1487

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Title

NOVEL COLCHICINE ANALOGUES TARGET MITOCHONDRIAL PT PORES USING FREE TUBULINS AND INDUCE ROS-MEDIATED APOPTOSIS IN CANCEROUS LYMPHOCYTES

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Keywords

B-ACUTE LYMPHOBLASTIC LEUKEMIA

MICROTUBULES INHIBITORS

MITOCHONDRIA

VDAC

CASPASE CASCADE

APOPTOSIS

Abstract

B-ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL) is the frequent pediatric malignity. Chemotherapy is the most practical approaches to deal with such malignancies. Microtubule-targeted agents are one of the most strategic drugs which formerly used in chemotherapy. Although colchicine-binding anti-tubulin agents exhibited promising effects in clinical trials, their exact mechanism of action is not fully understood. In this study, the effects of two newly synthesized of colchicine derivatives were investigated on cell viability of cancerous and normal lymphocytes. The viability test was carried out by MTT assay. APOPTOSIS vs. necrosis was measured by double staining with annexin V/PI, and caspase-3 as the ultimate mediator of apoptotic measured through the colorimetric assay. Parameters of MITOCHONDRIAl damage (ROS formation, MMP (Mitochondrial Membrane Potential) decline, MITOCHONDRIAl swelling, and cytochrome c release following treatment by colchicine derivatives. By focusing on MITOCHONDRIAl parameters, we showed that following treatment by two newly synthesized colchicine derivatives, APOPTOSIS is triggered in cancerous B-lymphocytes. We demonstrated these compounds could activate APOPTOSIS in cancerous lymphocytes by augmentation of reactive oxygen species (ROS), a decline in MITOCHONDRIAl membrane potential (MMP), MITOCHONDRIAl swelling, release of cytochrome c, and also caspase-3 activation. Considering the obtained evidence, these inhibitors could be the new therapeutic strategies in ALL treatment.

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APA: Copy

AGHVAMI, MARJAN, ESHGHI, PEYMAN, Zarei, Mohammad Hadi, AREFI, HADI, SATTARI, FATEMEH, ZARGHI, AFSHIN, & POURAHMAD, JALAL. (2018). NOVEL COLCHICINE ANALOGUES TARGET MITOCHONDRIAL PT PORES USING FREE TUBULINS AND INDUCE ROS-MEDIATED APOPTOSIS IN CANCEROUS LYMPHOCYTES. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 17(4), 1476-1487. SID. https://sid.ir/paper/288890/en

Vancouver: Copy

AGHVAMI MARJAN, ESHGHI PEYMAN, Zarei Mohammad Hadi, AREFI HADI, SATTARI FATEMEH, ZARGHI AFSHIN, POURAHMAD JALAL. NOVEL COLCHICINE ANALOGUES TARGET MITOCHONDRIAL PT PORES USING FREE TUBULINS AND INDUCE ROS-MEDIATED APOPTOSIS IN CANCEROUS LYMPHOCYTES. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2018;17(4):1476-1487. Available from: https://sid.ir/paper/288890/en

IEEE: Copy

MARJAN AGHVAMI, PEYMAN ESHGHI, Mohammad Hadi Zarei, HADI AREFI, FATEMEH SATTARI, AFSHIN ZARGHI, and JALAL POURAHMAD, “NOVEL COLCHICINE ANALOGUES TARGET MITOCHONDRIAL PT PORES USING FREE TUBULINS AND INDUCE ROS-MEDIATED APOPTOSIS IN CANCEROUS LYMPHOCYTES,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 17, no. 4, pp. 1476–1487, 2018, [Online]. Available: https://sid.ir/paper/288890/en

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