Kumari, Neema and Bhargava, Anamika and Rath, Subha Narayan
(2020)
T-type calcium channel antagonist, TTA-A2 exhibits anti-cancer properties in 3D spheroids of A549, a lung adenocarcinoma cell line.
Life Sciences, 260.
p. 118291.
ISSN 00243205
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Abstract
Despite the advanced cancer treatments, there is increased resistance to chemotherapy and subsequent mortality. In lack of reliable data in monolayer cultures and animal models, researchers are shifting to 3D cancer spheroids, which represents the in vivo robust tumour morphology. Calcium is essential in cell signalling and proliferation. It is found that T-type calcium channels (TTCCs) are overexpressed in various cancer cells, supporting their increased proliferation. Many of the TTCCs blockers available could target other channels besides TTCCs, which can cause adverse effects. Therefore, we hypothesise that TTA-A2, a highly selective blocker towards TTCCs, can inhibit the growth of cancer spheroids, and provide an anti-cancer and an adjuvant role in cancer therapy. Methods: We studied TTA-A2 and paclitaxel (PTX-control drug) in lung adenocarcinoma cell line- A549, cancer cells and human embryonic kidney cell line- HEK 293, control cell, in their monolayer and spheroids forms for viability, proliferation, morphology change, migration, and invasion-after 48–96 h of treatment. Key findings: Though the results varied between the monolayer and spheroids studies, we found both anti-cancer as well as adjuvant effect of TTA-A2 in both the studies. TTA-A2 was able to inhibit the growth, viability, and metastasis of the cancer cells and spheroids. Differences in the results of two modes might explain that why drugs tested successfully in monolayer culture fail in clinical trials. Significance: This study establishes the role of TTA-A2, a potent TTCC blocker as an anti-cancer and adjuvant drug in reducing the viability and metastasis of the cancer cells.
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