Adjuvant role of a T-type calcium channel blocker, TTA-A2, in lung cancer treatment with paclitaxel

Kumari, Neema and Giri, Pravin Shankar and Rath, Subha Narayan (2021) Adjuvant role of a T-type calcium channel blocker, TTA-A2, in lung cancer treatment with paclitaxel. Cancer Drug Resistance, 4 (4). pp. 1-12. ISSN 2578-532X

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Abstract

Aim: Chemoresistance is a prevalent issue in cancer treatment. Paclitaxel (PTX) is a microtubule-binding anticancer drug used in various cancer treatments. However, cancer cells often show chemoresistance against PTX with the help of P-glycoprotein (Pgp) - a drug efflux pump. It has also been observed that overexpressed T-type calcium channels (TTCCs) maintain calcium homeostasis in cancer cells, and calcium has a role in chemoresistance. Therefore, the aim of this study was to test the adjuvant role of TTA-A2, a TTCC blocker, in enhancing the anticancer effect of PTX on the A549 lung adenocarcinoma cell line. Methods: Morphology assay, calcium imaging assay, clonogenic assay, apoptosis assay, and real-time polymerase chain reaction (real-time PCR) were performed to find the adjuvant role of TTA-A2. Samples were treated with PTX at 10 nM concentration and TTA-A2 at 50 and 100 nM concentrations. PTX and TTA-A2 were used in the combination treatment at 10 and 100 nM concentrations, respectively. Results: Immunocytochemistry confirmed the expression of TTCC in A549 cells. Morphology assay showed altered morphology of A549 cells. The adjuvant role of TTA-A2 was observed in the calcium imaging assay in spheroids, in the clonogenic assay in monolayers, and in the apoptosis assay in both cultures. With real-time PCR, it was observed that, even though cells express the mRNA of Pgp, it is non-significant upon treatment with PTX and TTA-A2. Conclusion: TTA-A2 can be used as an adjuvant to reduce chemoresistance in cancer cells as well as to enhance the anticancer effect of the standard anticancer drug PTX. Being a potent TTCC inhibitor, TTA-A2 may also enhance the anticancer effects of other anticancer drugs. © The Author(s) 2021.

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IITH Creators:

IITH Creators	ORCiD
Rath, Subha Narayan	https://orcid.org/0000-0002-3414-2328

Item Type:

Article

Additional Information:

This work was supported by Impacting Research Innovation and Technology (project code: 5450), and University Grant Commission fellowship (Ref. no. 21/12/2014(ii)EU-V)

Uncontrolled Keywords:

Adjuvant; Lung adenocarcinoma; Paclitaxel; T-type calcium channel blocker; TTA-A2

Subjects:

Others > Biotechnology
Biomedical Engineering

Divisions:

Department of Biomedical Engineering

Depositing User:

. LibTrainee 2021

Date Deposited:

04 Aug 2022 09:14

Last Modified:

04 Aug 2022 09:14