In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells

Byun, Joon Seok; Sohn, Joo Mi; Leem, Dong Gyu; Park, Byeongyeon; Nam, Ji Hye; Shin, Dong Hyun; Shin, Ji Sun; Kim, Hyoung Ja; Lee, Kyung‐Tae; Lee, Jae Yeol

doi:10.1016/j.bmcl.2015.12.010

Cited by 30 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(D) The results showed that the expressions of N-cadherin and Vimentin in the A549 -29and A549 -33groups were lower than the control group. In addition, the expression of E-cadherin in the A549 -29and A549 -33groups was higher than the control group (magnification, x100 (20) also found that A549 cell activity was decreased by KCP10043F treatment to inhibit Ca 2+ expression levels, which was consistent with the results of the present study. Expression levels of apoptotic proteins were measured, which demonstrated that the knockdown of TMCO1 inhibited the expression level of Bcl-2.…”

Section: Discussionsupporting

confidence: 91%

Mechanism of transmembrane and coiled‑coil domain 1 in the regulation of proliferation and migration of A549 cells

et al. 2020

View full text Add to dashboard Cite

Bioinformatics analyses have shown that transmembrane and coiled-coil domain 1 (TMCO1) may be associated with lung adenocarcinoma. However, to the best of our knowledge, no current research has determined whether TMCO1 is involved in the development of lung adenocarcinoma. The present study aimed to identify the association between TMCO1 and lung adenocarcinoma. The present study demonstrated that the positive immunohistochemical staining of TMCO1 in lung adenocarcinoma tissues was significantly higher compared with paracarcinoma tissues. Additionally, knockdown of TMCO1 was demonstrated to downregulate B-cell lymphoma-2 protein expression levels and upregulate cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 protein expression levels in A549 cells. These changes resulted in decreased apoptosis of A549 cells uponTMCO1 downregulation. In addition, knockdown of TMCO1 decreased matrix metalloproteinase (MMP)-2 and MMP-9 expression levels. The expression of N-cadherin and vimentin also decreased. By contrast, the expression levels of E-cadherin protein increased. Knockdown of TMCO1 resulted in the inhibition of A549 cell migration. The results of the present study demonstrated that TMCO1 was associated with lung adenocarcinoma and that inhibition of TMCO1 expression levels negatively regulated the apoptosis and migration of lung adenocarcinoma cells. Therefore, the present study suggests the potential for TMCO1 to be used in the clinical treatment of lung adenocarcinoma.

show abstract

Section: Discussionsupporting

confidence: 91%

Mechanism of transmembrane and coiled‑coil domain 1 in the regulation of proliferation and migration of A549 cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Etoposide is an anticancer drug which is the topoisomerase II inhibitor [6,7]. Etoposide is used to treat lung cancer, testicular cancer, lymphoma or glioblastoma multiform [8]. Anticancer agents, such as etoposide, bleomycin and doxorubicin, damage the vascular endothelium.…”

Section: Introductionmentioning

confidence: 99%

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

et al. 2019

View full text Add to dashboard Cite

A series of nine tetrahydroacridine derivatives with iodobenzoic moiety were synthesized and evaluated for their cytotoxic activity against cancer cell lines-A549 (human lung adenocarcinoma), HT-29 (human colorectal adenocarcinoma) and somatic cell line-EA.hy926 (human umbilical vein cell line). All compounds displayed high cytotoxicity activity against A549 (IC 50 59.12-14.87 µM) and HT-29 (IC 50 17.32-5.90 µM) cell lines, higher than control agents-etoposide and 5-fluorouracil. Structure-activity relationship showed that the position of iodine in the substituent in the para position and longer linker most strongly enhanced the cytotoxic effect. Among derivatives, 1i turned out to be the most cytotoxic and displayed IC 50 values of 14.87 µM against A549 and 5.90 µM against HT-29 cell lines. In hyaluronidase inhibition assay, all compounds presented anti-inflammatory activity, however, slightly lower than reference compound. ADMET prediction showed that almost all compounds had good pharmacokinetic profiles. 1b, 1c and 1f compounds turned out to act against chemoresistance in cisplatin-resistant 253J B-V cells. Compounds intercalated into DNA and inhibited cell cycle in G0/G1 phase-the strongest inhibition was observed for 1i in A549 and 1c in HT-29. Among compounds, the highest apoptotic effect in both cell lines was observed after treatment with 1i. Compounds caused DNA damage and H2AX phosphorylation, which was detected in A549 and HT-29 cells. All research confirmed anticancer properties of novel tetrahydroacridine derivatives and explained a few pathways of their mechanism of cytotoxic action.

show abstract

“…In addition, antiparasitic activity has been studied for some members of this family as inhibitors of trypanothione reductase [ 5 ], an essential enzyme of the kinetoplastid Trypanosoma brucei. Their activity as selective T-type calcium channel blockers [ 6 – 11 ], as tumor suppressors [ 12 ] and as neuroprotective agents has also been reported [ 13 ]. Some related 2-amino-DHQs were studied as blood platelet aggregation inhibitors [ 14 ], antihypertensive agents [ 15 ] or inhibitors of β - secretase, an important target for Alzheimer’s disease [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

Gruber¹,

Díaz²,

Orelli³

2018

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

The sequential N-functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2-ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration reaction promoted by trimethylsilyl polyphosphate (PPSE) is also proposed on the basis of literature data and our experimental observations.

show abstract

In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells

Cited by 30 publications

References 31 publications

Mechanism of transmembrane and coiled‑coil domain 1 in the regulation of proliferation and migration of A549 cells

Mechanism of transmembrane and coiled‑coil domain 1 in the regulation of proliferation and migration of A549 cells

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

Contact Info

Product

Resources

About

In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells

Cited by 30 publications

References 31 publications

Mechanism of transmembrane and coiled‑coil domain 1 in the regulation of proliferation and migration of A549 cells

Mechanism of transmembrane and coiled‑coil domain 1 in the regulation of proliferation and migration of A549 cells

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N3-aryl derivatives with electron-withdrawing groups

Contact Info

Product

Resources

About

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups