Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway

Lin, Shiqi; Jia, Fu-Juan; Zhang, Caiyun; Liu, Fang-Yuan; Ma, Jiahui; Han, Ze‐Guang; Xie, Wenrui; Li, Xia

doi:10.3390/md17100572

Cited by 17 publications

(15 citation statements)

References 24 publications

(31 reference statements)

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“…Similar discrepancies in cell lines have been reported in several previous studies. There might exist one target signaling pathway involved in both NSCLC cell lines that was not discussed in our study, 34 pathways 35 or the innate difference between cell lines 35,36 might also account for the discrepancy, and further exploration is needed.…”

Section: Discussionmentioning

confidence: 87%

5-HT7 Receptor Contributes to Proliferation, Migration and Invasion in NSCLC Cells

Du¹,

Wang²,

Wang³

et al. 2020

OTT

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Introduction: Because only a small portion of NSCLC (non-small-cell lung cancer) patients benefit from molecular targeted therapy or immunotherapy and do not develop therapeutic resistance, continued research on new targets is warranted. Serotonin has recently emerged as a growth factor for tumor cells, and its receptors may be potential therapeutic targets. The mechanism related to the behavior of the 5-HT 7 receptor in NSCLC remains unknown. Methods: Both gene expression analysis and immunohistochemical analysis were conducted to evaluate 5-HT 7 receptor expression in NSCLC tissues. The correlation between 5-HT 7 receptor expression and clinicopathological features was also examined. Cell proliferation was measured using a CCK8 (Cell Counting Kit-8) assay and colony formation, migration and invasion were evaluated by the Transwell assay. siRNA transfection and stimulation with the selective agonist LP211 were used to identify the involvement of molecules in proliferation, migration and invasion. Quantitative real-time chain reaction (qRT-PCR) and Western blotting were used to quantifiy mRNA and protein levels, respectively. Pathway inhibitors facilitated the exploration of possible signaling pathways regulated by the 5-HT 7 receptor in migration and invasion. Results: The 5-HT 7 receptor was overexpressed in NSCLC tumor tissues compared with adjacent normal lung tissues. High 5-HT 7 receptor expression levels were correlated with lymph node metastasis (P=0.007) and advanced TNM stage (P=0.000) in NSCLC patients. The 5-HT 7 receptor positively regulated cell proliferation, migration and invasion in NSCLC cells. The stimulatory effect of the 5-HT 7 receptor on A549 cell migration and invasion may occur through the P38 pathway. In H1299 cells, the 5-HT 7 receptor might positively regulate Src to promote cell migration and invasion. Conclusion: Our findings suggest that the 5-HT 7 receptor, which mediates NSCLC progression, may be a potential therapeutic target.

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Section: Discussionmentioning

confidence: 87%

5-HT7 Receptor Contributes to Proliferation, Migration and Invasion in NSCLC Cells

Du¹,

Wang²,

Wang³

et al. 2020

OTT

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“…The cells were treated with serial concentrations of Act V and Act D (0–0.02 μM) for 48 h, and the IC 50 s were determined (Act D, which has been used for a long time in clinic, serves as a positive control here), as shown in Table 1 and our previous study [ 10 , 11 ]. Act V exhibited considerably stronger efficacy against cancer cells with a ten-fold lower IC 50 value compared to Act D. Act V and Act D induced cytotoxicity in human normal liver LO-2 and human embryonic kidney 293T cell lines in a concentration-dependent manner ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…[ 1 ], has a similar structure to that of Act D ( Figure 1 ). In our previous studies [ 10 , 11 ], Act V was found to be more cytotoxic to tumor cells than Act D. Moreover, Act V inhibited the migration and metastasis of breast cancer cells. In this aspect, Act V may be a potential substitute for Act D, so understanding the toxicological mechanisms of Act V and Act D is of great worth.…”

Section: Introductionmentioning

confidence: 93%

Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo

Jia

Han

et al. 2020

Marine Drugs

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The high toxicity of actinomycin D (Act D) severely limits its use as a first-line chemotherapeutic agent in the clinic. Actinomycin V (Act V), an analog of Act D, exhibited strong anticancer activity in our previous studies. Here, we provide evidence that Act V has less hepatorenal toxicity than Act D in vitro and in vivo, associated with the reactive oxygen species (ROS) pathway. Compared to Act D, Act V exhibited considerably stronger sensitivity for cancer cells and less toxicity to human normal liver LO-2 and human embryonic kidney 293T cells using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Notably, Act V caused less damage to both the liver and kidney than Act D in vivo, indicated by organ to body weight ratios, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (Scr) levels. Further experiments showed that the ROS pathway is involved in Act V-induced hepatorenal toxicity. Act V generates ROS and accumulates malondialdehyde (MDA), reducing levels of superoxide dismutase (SOD) and glutathione (GSH) in LO-2 and 293T cells. These findings indicate that Act V induces less hepatorenal toxicity than Act D in vitro and in vivo and merits further development as a potential therapeutic agent for the treatment of cancer.

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“…45 TP53 functions as a transcription activator of other targets downstream, including p21 and Bax, signifying that p53 can activate different pathways, including apoptosis. 45–47 Previous studies have demonstrated CP 's ability to impede various types of human cancer cell growth via alteration of key apoptotic signaling pathways. 20,48…”

Section: Discussionmentioning

confidence: 99%

Calliandra portoricensisameliorates ovarian and uterine oxido-inflammatory responses inN-methyl-N-nitrosourea and benzo[a]pyrene-treated rats

Adefisan

Madu

Owumi

et al. 2020

Exp Biol Med (Maywood)

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Reproductive dysfunction stemming from chemical agents may lead to infertility. We examined the protective effects of Calliandra portoricensis ( CP) extract on benzo[a]pyrene (BaP) and N-methyl- N-nitrosourea (NMU)-induced ovarian and uterine toxicity in rat, treated as follows: control (group 1), NMU + BaP (group 2), groups 3 and 4 received (NMU + BaP), and CP (50 and 100 mg/kg), respectively. Group 5: CP (100 mg/kg) alone, group 6: (NMU + BaP) and vincristine (VIN: 0.5 mg/kg) and group 7: VIN alone. Rats were injected at age 7, 10, and 13 weeks with single doses of NMU and BaP for 10 consecutive weeks. NMU + BaP significantly ( P < 0.05) increased ovarian and uterine weight, and decreased bodyweight, while the organo-somatic index (OSI) of uterus and ovary increased 2.3 and 1.4 folds, respectively. CP co-treatment ameliorated the observed weight changes. Lipid peroxidation increased by 58% in the ovary, accompanied by decreases in ovarian and uterine GST, GPx, catalase activities, and total sulfhydryl level in NMU + BaP-treated rats. Uterine and ovarian myeloperoxidase activities, as well as nitric oxide levels also increased. CP co-treatment ameliorated the observed changes in antioxidant enzymes and inflammatory biomarkers. Furthermore, histopathology revealed fibrotic ovarian stroma, while uterine endometrium was infiltrated with inflamed cells. Immunohistochemistry showed weak expression of FSH, LH, p53, caspase-3, and Bax, whereas progesterone, iNOS, and Bcl-2 were strongly expressed in NMU + BaP-treated rats. CP treatment restored the architecture of these tissues. Conclusively, the root bark fraction of CP decreases oxido-inflammatory damage in ovarian and uterine tissues of NMU- and BaP-treated rats. Impact statement Infertility resulting from reproductive impairment is traumatic in families. Exposure to chemicals may play insidious roles not easily connected to infertility. We examined benzo[a]pyrene (BaP), and N-methyl nitrosourea (NMU)-induced ovarian and uterine toxicity and the role of Calliandra portoricensis in mitigating toxicity. In a bid to illuminate folk medical claims cloaked in mystery, unearthing lost knowledge, advance natural chemopreventive agents, and report new evidence lacking in the literature attributed to CP. Although CP is known to exhibit anticonvulsant, antidiarrheal, antipyretic, antirheumatic, and analgesic effects in humans, its possible roles for mitigating toxicity stemming from inadvertent chemical exposures are reported here. Our findings affirm and further show that CP abates toxic response incumbent on oxidative damage and inflammatory responses associated with NMU and BaP exposure. Development of phytochemical derived from CP may serve as a potential natural therapy against chemical toxicities in individuals inadvertently exposed, and promote human health and reproductive satiety.

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Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway

Cited by 17 publications

References 24 publications

<p>5-HT<sub>7</sub> Receptor Contributes to Proliferation, Migration and Invasion in NSCLC Cells</p>

<p>5-HT<sub>7</sub> Receptor Contributes to Proliferation, Migration and Invasion in NSCLC Cells</p>

Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo

Calliandra portoricensisameliorates ovarian and uterine oxido-inflammatory responses inN-methyl-N-nitrosourea and benzo[a]pyrene-treated rats

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