8-methoxypsoralen reduces AKT phosphorylation, induces intrinsic and extrinsic apoptotic pathways, and suppresses cell growth of SK-N-AS neuroblastoma and SW620 metastatic colon cancer cells

Bartnik, Magdalena; Sławińska-Brych, Adrianna; Żurek, Aleksandra; Kandefer‐Szerszeń, Martyna; Zdzisińska, Barbara

doi:10.1016/j.jep.2017.06.010

Cited by 38 publications

(36 citation statements)

References 66 publications

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“…In apoptosis, cytosol Bax releases caspase-activating Cyt-c. The caspase-8 (extrinsic apoptosis) or -9 (intrinsic apoptosis), is activated which further activates caspase-3, essential to propagates apoptotic signal [49][50][51][52][53]. Cell shrinkage and chromatin condensation helps in apoptosis [54].…”

Section: Pi3k/akt Inhibitionmentioning

confidence: 99%

“…It also induced apoptosis, G1 phase arrest, DNA fragmentation, and downregulation of PI3K/Akt/m-TOR signaling pathway [58]. Methoxsalen (8-MOP) activated caspase-8 -9, Bax/Bcl-2 ratio upregulation, cytochrome-c (Cyt-c) release, and CREB phosphorylation decrement to down-regulates Bcl-2 for apoptosis in SW620 and SK-N-AS cells, through PI3K/Akt down-regulation [51]. Angelicin increases Bax, caspase-3, -9, decreases Bcl-2, Bcl-xL, Mcl-1 in A549 (NSCLC) cells [33], and SH-SY5Y cells [59] to induce intrinsic mitochondria-mediated apoptosis.…”

Section: Pi3k/akt Inhibitionmentioning

confidence: 99%

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Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Ahmed

Khan

Aschner

et al. 2020

IJMS

128

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Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins’ defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents.

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Section: Pi3k/akt Inhibitionmentioning

confidence: 99%

Section: Pi3k/akt Inhibitionmentioning

confidence: 99%

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Ahmed

Khan

Aschner

et al. 2020

IJMS

128

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“…The quantitative analysis of AKG-induced cell death was performed using an Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis kit (BD Biosciences, BD Pharmingen™, San Jose, CA, USA) and the flow cytometry method as described previously [73]. Briefly, the Saos-2 or HOS cells were seeded into 6-well plates at a density of 7 × 10 5 cells/well.…”

Section: Flow Cytometrymentioning

confidence: 99%

Alpha Ketoglutarate Exerts In Vitro Anti-Osteosarcoma Effects through Inhibition of Cell Proliferation, Induction of Apoptosis via the JNK and Caspase 9-Dependent Mechanism, and Suppression of TGF-β and VEGF Production and Metastatic Potential of Cells

Kaławaj

Sławińska-Brych

Mizerska-Kowalska

et al. 2020

IJMS

Self Cite

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Osteosarcoma (OS) is the most common type of primary bone tumor. Currently, there are limited treatment options for metastatic OS. Alpha-ketoglutarate (AKG), i.e., a multifunctional intermediate of the Krebs cycle, is one of the central metabolic regulators of tumor fate and plays an important role in cancerogenesis and tumor progression. There is growing evidence suggesting that AKG may represent a novel adjuvant therapeutic opportunity in anti-cancer therapy. The present study was intended to check whether supplementation of Saos-2 and HOS osteosarcoma cell lines (harboring a TP53 mutation) with exogenous AKG exerted an anti-cancer effect. The results revealed that AKG inhibited the proliferation of both OS cell lines in a concentration-dependent manner. As evidenced by flow cytometry, AKG blocked cell cycle progression at the G1 stage in both cell lines, which was accompanied by a decreased level of cyclin D1 in HOS and increased expression of p21Waf1/Cip1 protein in Saos-2 cells (evaluated with the ELISA method). Moreover, AKG induced apoptotic cell death and caspase-3 activation in both OS cell lines (determined by cytometric analysis). Both the immunoblotting and cytometric analysis revealed that the AKG-induced apoptosis proceeded predominantly through activation of an intrinsic caspase 9-dependent apoptotic pathway and an increased Bax/Bcl-2 ratio. The apoptotic process in the AKG-treated cells was mediated via c-Jun N-terminal protein kinase (JNK) activation, as the specific inhibitor of this kinase partially rescued the cells from apoptotic death. In addition, the AKG treatment led to reduced activation of extracellular signal-regulated kinase (ERK1/2) and significant inhibition of cell migration and invasion in vitro concomitantly with decreased production of pro-metastatic transforming growth factor β (TGF-β) and pro-angiogenic vascular endothelial growth factor (VEGF) in both OS cell lines suggesting the anti-metastatic potential of this compound. In conclusion, we showed the anti-osteosarcoma potential of AKG and provided a rationale for a further study of the possible application of AKG in OS therapy.

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“…Linear furanocoumarins have drawn attention in recent years as potential anti-cancer agents, either alone or in combination with other drugs. It has been shown that xanthotoxin and bergapten, independently of photoactivation, inhibit the growth of neuroblastoma, colon cancer cells [10], melanoma [11], hepatoma [12], and breast cancer cells [13]. Furanocoumarins such as imperatorin and bergamottin have been found to significantly enhance the cytotoxicity of cisplatin to hepatocellular carcinoma (HCC) cells [14] and potentiate the apoptotic effects of bortezomid and thalidomide in multiple myeloma (MM) cells [15].…”

Section: Introductionmentioning

confidence: 99%

Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

et al. 2020

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Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

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8-methoxypsoralen reduces AKT phosphorylation, induces intrinsic and extrinsic apoptotic pathways, and suppresses cell growth of SK-N-AS neuroblastoma and SW620 metastatic colon cancer cells

Cited by 38 publications

References 66 publications

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Alpha Ketoglutarate Exerts In Vitro Anti-Osteosarcoma Effects through Inhibition of Cell Proliferation, Induction of Apoptosis via the JNK and Caspase 9-Dependent Mechanism, and Suppression of TGF-β and VEGF Production and Metastatic Potential of Cells

Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

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