Implication of methylselenocysteine in combination chemotherapy with gemcitabine for improved anticancer efficacy.

Autor: Behera C; PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu180001, India; Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab143001, India., Sandha KK; PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Banjare N; PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Malik SB; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India., Tabassum M; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India., Kumar R; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India., Kumar A; Instrumentation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India., Mondhe DM; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: dmmondhe@iiim.res.in., Gupta PN; PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: pngupta@iiim.res.in.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2022 Sep 01; Vol. 176, pp. 106238. Date of Electronic Publication: 2022 Jun 14.
DOI: 10.1016/j.ejps.2022.106238
Abstrakt: The limitations associated with cancer monotherapy including dose dependent toxicity and drug resistance can be addressed by combination chemotherapy. The combination of antineoplastic agents improves the cytotoxic activity in comparison to the single-agent based therapy in a synergistic or an additive mode by reducing tumor growth as well as metastatic ability. In the present investigation, we explored the potential of methylselenocysteine (MSC) in combination chemotherapy with gemcitabine (GEM). The cytotoxic activity of GEM and MSC was determined in various cell lines and based on the activity, A549 cells were explored for the mechanistic studies including DAPI staining, measurement of oxidative stress, mitochondrial membrane potential loss, nitric oxide level, western blotting, cell migration and colony formation assays. A549 cells in combination treatment with MSC and GEM demonstrated enhanced cytotoxicity with more irregular cellular morphology as well as chromatin condensation and nuclear blebbing. The selected combination also significantly triggered ROS generation and mitochondrial destabilization, and alleviated cell migration potential and clonogenic propensity of A549 cells. Also, caspase-3 and PARP mediated apoptosis was observed in the combination treated cells. MSC based drug combination could offer the attributes of improved drug delivery and there was a 6-folds dose reduction of GEM in combination. Further, antitumor study in Ehrlich solid tumor model showed the efficacy of MSC combination with GEM for the enhanced antitumor activity. The proposed combination demonstrated the potential for further translational studies.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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