• Biomolecules & Therapeutics
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• 제26권4호
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• pp.409-416
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• 2018

Vasicinone, a quinazoline alkaloid from Adhatoda vasica Nees. is well known for its bronchodilator activity. However its anti-proliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, $70{\mu}M$) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. The Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells. Moreover vasicinone treatment also lead to down regulation of Bcl-2, Fas death receptor and up regulation of PARP, BAD and cytochrome c, suggesting the anti-proliferative nature of vasicinone which mediated apoptosis through both Fas death receptors as well as Bcl-2 regulated signaling. Furthermore, our preliminary studies with vasicinone treatment also showed to lower the ROS levels in A549 cells and have potential free radical scavenging (DPPH, Hydroxyl) activity and ferric reducing power in cell free systems. Thus combining all, vasicinone may be used to develop a new therapeutic agent against oxidative stress induced lung cancer.

• 동의생리병리학회지
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• 제21권4호
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• pp.973-981
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• 2007

In the present study, we investigated the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines. We found that exposure of A549 cells to SGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, however SGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. SGBPT treatment did not induce the cell cycle arrest in both cell lines, however the frequency of sub-G1 population was concentration-dependently increased by SGBPT treatment in A549 cells. SGBPT treatment partially induced the expression of tumor suppressor p53 in A549 cells and the expression of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was markedly increased in both transcriptional and translational levels in A549 cells. The up-regulation of p21 by SGBPT occurred in a similar a concentration dependent manner to that observed with the inhibition of cell viability and induction of sub-G1 population of the cell cycle. However SGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), inducible nitric oxide synthease (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 as well as NCI-H460 cells. Taken together, these findings suggested that SGBPT-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the induction of p21 and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

• 동의생리병리학회지
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• 제17권2호
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• pp.451-456
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• 2003

We investigated the effects of Sabaek-san (SBS) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with SBS extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis. including condensation of chromatin. Flow cytometry analysis confirmed that SBS treatment increased populations of apoptotic-sub G1 phase. In addition. proteolytic cleavages of poly(ADP-ribose) polymerase and β-catenin protein were observed after treatment of SBS extract. These apoptotic effects of SBS in A549 cells were associated with marked inhibition of Bcl-2 and Bel-xL mRNA in a dose-dependent manner. however the levels of Bax expression were not affected, SBS treatment also induced a proteolytic activation of caspase-3. which is believed to play a central role In the apoptotic signaling pathway. The previous and present results indicated that SBS-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5895-5900
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• 2013

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

• 동의생리병리학회지
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• 제19권3호
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• pp.722-728
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• 2005

The DNA topoismerase I inhibitor ${\beta}-lapachone$, the product of a lapacho tree (Tabebuia avellanedae) from South America, activates a novel apoptotic response in a number of cell lines. In the present report, we investigated the effects of ${\beta}-lapachone$ on the growth of human lung in human non-small-cell-lung-cancer A549 cells. Upon treatment with ${\beta}-lapachone$, a concentration-dependent inhibition of cell viability and cell proliferation was observed as measured by hemocytometer counts and MTT assay. The ${\beta}-lapachone-treated$ cells developed many of the hallmark features of apoptosis, including membrane shrinking, condensation of chromatin and DNA fragmentation. These apoptotic effects of ${\beta}-lapachone$ in A549 cells were associated with a marked induction of pro-apoptotic Bax expression, however the levels of anti-apoptotic Bcl-2 expression were decreased in a dose-dependent manner. Accordingly, elevated amount of cyclin-dependent kinase inhibitor p21 expression accompanied by up-regulation of tumor suppressor p53 was observed. By RT-PCR analyses, decrease in gene expression level of telomerase reverse transcriptase and telomeric repeat binding factor were also observed. Thus, these findings suggest that ${\beta}-lapachone$ may be a potential anti-cancer therapeutics for the control of human lung cancer cell model.

• 동의생리병리학회지
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• 제17권3호
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• pp.677-683
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• 2003

We investigated the effects of Insamsapye-tang (ISSPT) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with ISSPT extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that ISSPT treatment increased populations of apoptotic-sub G1 phase. In addition, proteolytic degradation of poly(ADP-ribose) polymerase (PARP) and β-catenin protein were observed after treatment of ISSPT extract. These apoptotic effects of ISSPT in A549 cells were associated with marked inhibition of Bel-xL expression in a dose-dependent manner, however the levels of Bcl-2 and Bax expression were not affected. ISSPT treatment also induced the expression of tumor suppressor p53 mRNA and inhibited the expression of caspase-3 mRNA. The previous and present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 춘계학술대회
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• pp.93-93
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on GSK3${\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• 대한의생명과학회지
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• 제28권4호
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• pp.247-259
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• 2022

Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

• 생명과학회지
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• 제14권5호
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• pp.800-808
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• 2004

Resveratrol은 포도와 같은 식물에서 각종 감염균으로부터 자신의 몸을 보호하기 위하여 생성되는 물질인 phytoalexin의 일종으로 강력한 항산화작용, 암예방 효과 및 항암 작용을 포함한 각종 약리작용을 가진 것으로 보고되어져 오고 있다. 본 연구에서는 resveratrol의 항암작용 기전해석을 위하여 A549 인체폐암세포의 종식에 미치는 resverakol의 영향을 조사하였다. A549 세포의 생존율은 resveratrol의 처리시간 증가에 따라 강력하게 억제되었으며, 이는 암세포의 다양한 형태변형을 동반한 세포주기 C2/M arrest 및 염색질 응축 현상을 동반한 apoptosis 유발에 의한 것임을 알 수 있었다. Resveratrol 처리에 의한 apoptosis 유발은 Bcl-2의 발현변화 없이 Bcl-$X_L$의 발현 감소에 따른 상대적인 Bax의 발현 증가와 Sp-1, PCNA 및 $\beta$-catenin 등과 같은 단백질의 분해 현상과 연관성이 있었다 또한 resveratrol에 의한 A549세포 의 증식억제는 Cdk inhibitor p21의 발현 증가에 따른 Cdks 의 kinase 활성 저하 및 COX-2의 선택적 저해에 따른 PGE2 생성 저하와 관련이 있었다.

• 동의생리병리학회지
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• 제18권3호
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• pp.759-766
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• 2004

In the present study, we investigated the effects of aqueous extract of the healthful decoction utilizing Phellinus linteus (HDPL) on the cell growth of human lung carcinoma tumor cell line A549. Exposure of A549 cells to HDPL resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometric analysis. This increase in apoptosis was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase (PARP), b-catenin and phospholipase C- 1 (PLC- 1) protein. HDPL treatment induced the down-regulation of anti-apoptotic Bcl-2 expression, an anti-apoptotic gene, however, the level of Bax. a pro-apoptotic gene, was increased by HDPL treatment. In addition, HDPL-induced apoptotis of A549 cells was connected with activation of caspase-3 and caspase-9 protease in a dose-dependent manner, however, the levels of inhibitor of apoptosis proteins family were remained unchanged. Taken together, these results indicated that the anti-proliferative effects of HDPL were associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease activity, and HDPL may have therapeutic potential in human lung cancer.