Combining α-Hederin with cisplatin increases the apoptosis of gastric cancer in vivo and in vitro via mitochondrial related apoptosis pathway

Deng, Huan; Ma, Jingjing; Liu, Yinghui; He, Pengzhan; Dong, Weiguo

doi:10.1016/j.biopha.2019.109477

Cited by 21 publications

(20 citation statements)

References 32 publications

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“…UNC0638 was obtained from Selleck and dissolved in dimethyl sulfoxide at 5 mM for stock solution, which was stored at −20°C. All experiments were performed in mycoplasma-free condition [21].…”

Section: Methodsmentioning

confidence: 99%

“…Finally, the membranes were scanned using a two-color Odyssey infrared imaging system (LI-COR Biosciences). Protein bands were quantified by densitometry using the ImageJ software (National Institutes of Health, Bethesda, MD, USA) [21].…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

“…After 80 μl cell suspensions were added, the plates were incubated at 37°C for 24 h. The cells, which invaded into the lower layer, were washed with phosphate-buffered saline, fixed with methanol, and stained with 1% crystal violet. Invasive cells were counted in five random fields for each well by an inverted microscope (BX51; Olympus Corporation) [21]. 3 Oxidative Medicine and Cellular Longevity 2.9.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

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Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5

Deng

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Renal cell carcinoma (RCC) accounts for approximately 2–3% of malignant tumors in adults, while clear cell renal cell carcinoma accounts for 70–85% of kidney cancer cases, with an increasing incidence worldwide. G9a is the second histone methyltransferase found in mammals, catalyzing lysine and histone methylation. It regulates gene transcription by catalyzing histone methylation and interacting with transcription factors to alter the tightness of histone-DNA binding. The main purpose of this study is to explore the role and mechanism of G9a in renal cell carcinoma. Methods. Firstly, we investigated the expression of G9a in 80 clinical tissues and four cell lines. Then, we explored the effect of G9a-specific inhibitor UNC0638 on proliferation, apoptosis, migration, and invasion of two renal cancer cell lines (786-O, SN12C). In order to study the specific mechanism, G9a knocking down renal cancer cell line was constructed by lentivirus. Finally, we identified the downstream target genes of G9a using ChIP experiments and rescue experiments. Results. The results showed that the specific G9a inhibitor UNC0638 significantly inhibited the proliferation, migration, and invasion of kidney cancer in vivo and in vitro; similar results were obtained after knocking down G9a. Meanwhile, we demonstrated that SPINK5 was one of the downstream target genes of G9a through ChIP assay and proved that G9a downregulate the expression of SPINK5 by methylation of H3K9me2. Therefore, targeting G9a might be a new approach to the treatment of kidney cancer. Conclusion. G9a was upregulated in renal cancer and could promote the development of renal cancer in vitro and in vivo. Furthermore, we identified SPINK5 as one of the downstream target genes of G9a. Therefore, targeting G9a might be a new treatment for kidney cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Cell Proliferation Assaymentioning

confidence: 99%

Section: Cell Proliferation Assaymentioning

confidence: 99%

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Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5

Deng

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…The apoptotic cells were analyzed by Hoechst staining as previously described [ 15 ]. Briefly, 24 h after the induction of MXD-medicated serum and PM2.5, cells were incubated with Hoechst 33258 (Wanleibio, China) at room temperature for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Ma xing shi gan decoction eliminates PM2.5-induced lung injury by reducing pulmonary cell apoptosis through Akt/mTOR/p70S6K pathway in rats

Wang¹,

Zhao

Fei

et al. 2020

Bioscience Reports

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Abstract The present study was designed to investigate the anti-apoptosis effect of Ma xing shi gan decoction (MXD) on PM2.5-induced lung injury via protein kinase B (Akt)/mTOR/p70S6K pathway. A UPLC-MS/MS system was introduced for component analysis of MXD. Rats were instilled with PM2.5 solution suspension intratracheally to induce acute lung injury. The rats were then orally administered with MXD (16, 8, and 4 g/kg) once a day for 7 consecutive days. The therapeutic effects of MXD were evaluated by Hematoxylin and Eosin (HE) staining. The apoptotic cell death was analyzed by terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay. The alterations in cytochrome c (Cytc) and cleaved-caspase-3 (C-caspase-3) were measured by immunohistochemistry (IHC). The expressions of Bax, B-cell lymphoma 2 (Bcl-2), p-Akt, p-mTOR and p-p70S6K were detected by Western blot. In vitro, PM2.5 exposure model was introduced in A549 cell, followed by incubation with MXD-medicated serum. Hoechst staining was used to determine apoptotic rate. The levels of Bax, Bcl-2, p-Akt, p-mTOR and p-p70S6K were detected by Western blot. Our results in vivo indicated that treatment with MXD decreased histopathological changes score, TUNEL-positive cells rate, expressions of Cytc and C-caspase-3. The in vitro results revealed that incubation with MXD-mediated serum decreased apoptotic rate. Both results in vivo and in vitro demonstrated that MXD inhibited pro-apoptotic protein Bax and promoted anti-apoptotic protein Bcl-2 expression. Likewise, MXD activated Akt/mTOR/p70S6K signal pathway, which was also confirmed by Western immunoblotting. In conclusion, MXD attenuates lung injury and the underlying mechanisms may relate to regulating the apoptosis via Akt/mTOR/p70S6K signaling pathway activation.

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“…Combining ginsenoside compound K with cisplatin produced a better effect on the apoptosis and epithelial mesenchymal transition through the PI3K/Akt pathway in MCF-7 cells [162]. The combined effect of α-Hederin and cisplatin was better than both compounds alone on apoptosis by increasing ROS and decreasing MMP in vitro and vivo [163]. Berberine [164], cernumidine [144], shikonin [165], gallic acid [131,166], and dehydrobruceine b [167] also had a chemosensitizing effect when added together with cisplatin.…”

Section: Natural Products and Anticancer Agents In Combinationmentioning

confidence: 99%

Natural Products Targeting the Mitochondria in Cancers

Yang

Zhang

et al. 2020

Molecules

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There are abundant sources of anticancer drugs in nature that have a broad prospect in anticancer drug discovery. Natural compounds, with biological activities extracted from plants and marine and microbial metabolites, have significant antitumor effects, but their mechanisms are various. In addition to providing energy to cells, mitochondria are involved in processes, such as cell differentiation, cell signaling, and cell apoptosis, and they have the ability to regulate cell growth and cell cycle. Summing up recent data on how natural products regulate mitochondria is valuable for the development of anticancer drugs. This review focuses on natural products that have shown antitumor effects via regulating mitochondria. The search was done in PubMed, Web of Science, and Google Scholar databases, over a 5-year period, between 2015 and 2020, with a keyword search that focused on natural products, natural compounds, phytomedicine, Chinese medicine, antitumor, and mitochondria. Many natural products have been studied to have antitumor effects on different cells and can be further processed into useful drugs to treat cancer. In the process of searching for valuable new drugs, natural products such as terpenoids, flavonoids, saponins, alkaloids, coumarins, and quinones cover the broad space.

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Combining α-Hederin with cisplatin increases the apoptosis of gastric cancer in vivo and in vitro via mitochondrial related apoptosis pathway

Cited by 21 publications

References 32 publications

Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5

Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5

Ma xing shi gan decoction eliminates PM2.5-induced lung injury by reducing pulmonary cell apoptosis through Akt/mTOR/p70S6K pathway in rats

Natural Products Targeting the Mitochondria in Cancers

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