The Induction of Apoptosis in A375 Malignant Melanoma Cells bySutherlandia frutescens

Sutherlandia frutescensis a medicinal plant indigenous to Southern Africa and is commonly known as the “cancer bush.” This plant has traditionally been used for the treatment of various ailments, although it is best known for its claims of activity against “internal” cancers. Here we report on its effect on melanoma cells. The aim of this study was to investigate whether an extract ofS. frutescenscould induce apoptosis in the A375 melanoma cell line and to outline the basic mechanism of action.S. frutescensextract induced apoptosis in A375 cells as evidenced by morphological features of apoptosis, phosphatidylserine exposure, nuclear condensation, caspase activation, and the release of cytochromecfrom the mitochondria. Studies in the presence of a pan-caspase inhibitor allude to caspase-independent cell death, which appeared to be mediated by the apoptosis inducing factor. Taken together, the results of this study show thatS. frutescensextract is effective in inducing apoptosis in malignant melanoma cells and indicates that furtherin vivomechanistic studies may be warranted.

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Berberine-photodynamic induced apoptosis by activating endoplasmic reticulum stress-autophagy pathway involving CHOP in human malignant melanoma cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.02.147 ◽

2021 ◽

Vol 552 ◽

pp. 183-190

Author(s):

Jiaping Fang ◽

Xuan Huang ◽

Yun Yang ◽

Xiaotong Wang ◽

Xin Liang ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Malignant Melanoma ◽

Endoplasmic Reticulum Stress ◽

Melanoma Cells ◽

Human Malignant Melanoma ◽

Autophagy Pathway ◽

Induced Apoptosis

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A Novel Fast Photothermal Therapy Using Hot Spots of Gold Nanorods for Malignant Melanoma Cells

Nanomaterials ◽

10.3390/nano8110880 ◽

2018 ◽

Vol 8 (11) ◽

pp. 880 ◽

Cited By ~ 3

Author(s):

Yanhua Yao ◽

Nannan Zhang ◽

Xiao Liu ◽

Qiaofeng Dai ◽

Haiying Liu ◽

...

Keyword(s):

Cell Death ◽

Malignant Melanoma ◽

Gold Nanorods ◽

Plasmon Resonance ◽

Photothermal Therapy ◽

Treatment Time ◽

High Energy ◽

Melanoma Cells ◽

Photothermal Effect ◽

A375 Cells

In this paper, the plasmon resonance effects of gold nanorods was used to achieve rapid photothermal therapy for malignant melanoma cells (A375 cells). After incubation with A375 cells for 24 h, gold nanorods were taken up by the cells and gold nanorod clusters were formed naturally in the organelles of A375 cells. After analyzing the angle and space between the nanorods in clusters, a series of numerical simulations were performed and the results show that the plasmon resonance coupling between the gold nanorods can lead to a field enhancement of up to 60 times. Such high energy localization causes the temperature around the nanorods to rise rapidly and induce cell death. In this treatment, a laser as low as 9.3 mW was used to irradiate a single cell for 20 s and the cell died two h later. The cell death time can also be controlled by changing the power of laser which is focused on the cells. The advantage of this therapy is low laser treatment power, short treatment time, and small treatment range. As a result, the damage of the normal tissue by the photothermal effect can be greatly avoided.

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Inhibition of CaMKII-mediated c-FLIP expression sensitizes malignant melanoma cells to TRAIL-induced apoptosis

Experimental Cell Research ◽

10.1016/j.yexcr.2004.11.002 ◽

2005 ◽

Vol 304 (1) ◽

pp. 244-255 ◽

Cited By ~ 40

Author(s):

C XIAO ◽

B FENGYANG ◽

J SONG ◽

H SCHULMAN ◽

L LI ◽

...

Keyword(s):

Malignant Melanoma ◽

Melanoma Cells ◽

Induced Apoptosis

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Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo.

The Journal of Cell Biology ◽

10.1083/jcb.135.6.1889 ◽

1996 ◽

Vol 135 (6) ◽

pp. 1889-1898 ◽

Cited By ~ 75

Author(s):

D Schadendorf ◽

M A Kern ◽

M Artuc ◽

H L Pahl ◽

T Rosenbach ◽

...

Keyword(s):

Cell Death ◽

Malignant Melanoma ◽

Programmed Cell Death ◽

Melanoma Cells ◽

Human Melanoma ◽

Mrna Levels ◽

Synthetic Retinoid ◽

Human Melanoma Cells

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.

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The Efficacy of Dandelion Root Extract in Inducing Apoptosis in Drug-Resistant Human Melanoma Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/129045 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

S. J. Chatterjee ◽

P. Ovadje ◽

M. Mousa ◽

C. Hamm ◽

S. Pandey

Keyword(s):

Surgical Excision ◽

Natural Compounds ◽

Melanoma Cells ◽

Human Melanoma ◽

Root Extract ◽

Nuclear Condensation ◽

Apoptotic Pathway ◽

Outer Leaflet ◽

Human Melanoma Cells ◽

A375 Cells

Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25–29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS) generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.

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Polyphenol-rich extract induces apoptosis with immunogenic markers in melanoma cells through the ER stress-associated kinase PERK

Cell Death Discovery ◽

10.1038/s41420-019-0214-2 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 7

Author(s):

Karol Prieto ◽

Yu Cao ◽

Eslam Mohamed ◽

Jimena Trillo-Tinoco ◽

Rosa A. Sierra ◽

...

Keyword(s):

Er Stress ◽

Stress Responses ◽

Calcium Release ◽

Melanoma Cells ◽

Melanoma Tumor ◽

Cancer Cell Death ◽

Extracellular Release ◽

Induced Apoptosis ◽

Stress Mediators

Abstract Polyphenols elicit antitumor activities, in part, through the induction of anti- or pro-oxidant effects in cancer cells which promote priming of protective anti-tumor immunity. We recently characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) that stimulates in vivo antitumor responses against breast and melanoma tumor models via the promotion of immunogenic cancer cell death (ICD). However, the primary mediators whereby P2Et promotes ICD remained unknown. Here, we sought to elucidate the role that severe endoplasmic reticulum (ER) stress plays in mediating P2Et-induced apoptosis and ICD in murine melanoma cells. Our findings demonstrate a substantial selective induction of specific ER-stress mediators in B16-F10 melanoma cells treated with P2Et. While knockout of the ER stress-associated PKR-like ER kinase (PERK) prevented induction of apoptosis and expression of ICD markers in P2Et-treated cells, deletion of X-box binding protein 1 (Xbp1) did not. P2Et-driven activation of PERK in melanoma cells was found to promote ER-calcium release, disrupt mitochondrial membrane potential, and trigger upregulation of ICD drivers, surface calreticulin expression, and extracellular release of ATP and HMGB1. Notably, calcium release inhibition, but not targeting of PERK-driven integrated stress responses, prevented P2Et-induced apoptosis. Collectively, these results underline the central role of PERK-directed calcium release in mediating the antitumor and immunogenic actions of P2Et in melanoma cells.

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Capsaicin Exerts Therapeutic Effects by targeting tNOX-SIRT1 Axis and Augmenting ROS-Dependent Cytotoxic Autophagy in Melanoma Cancer Cells

10.21203/rs.3.rs-117713/v1 ◽

2020 ◽

Author(s):

Atikul Islam ◽

Pei-Fang Hsieh ◽

Jou-Chun Chou ◽

Jiunn-Wang Liao ◽

Ming-Kun Hsieh ◽

...

Keyword(s):

Malignant Melanoma ◽

Cancer Cells ◽

Nadh Oxidase ◽

Treatment Options ◽

Melanoma Cells ◽

Therapeutic Effects ◽

Melanoma Cancer ◽

Anticancer Properties

Abstract Background: Although considered a rare form of skin cancer, malignant melanoma has steadily increased internationally and is a main cause of cancer-associated death worldwide. The treatment options for malignant melanoma are very limited. Accumulating data suggest that the natural compound, capsaicin, exhibits preferential anticancer properties to act as a nutraceutical agent. Here, we explored the underlying molecular events involved in the inhibitory effects of capsaicin on the growth of melanoma cells.Methods: The cellular thermal shift assay (CETSA) and isothermal dose response fingerprint (ITDRFCETSA) were utilized to validate the binding of capsaicin with the tumor-associated NADH oxidase, tNOX (ENOX2) in melanoma cells. We also assessed the cellular impact of capsaicin-targeting of tNOX on A375 cells by flow cytometry and protein analysis. The essential role of tNOX in tumor- and melanoma-growth limiting abilities of capsaicin was evaluated in C57BL/6 mice.Results: Our data show that capsaicin directly targets cellular tNOX to inhibit its enzymatic activity and enhance protein degradation capacity. The inhibition of tNOX by capsaicin is accompanied by the attenuation of SIRT1, a NAD+-dependent deacetylase that enhances ULK1 acetylation to induce ROS-dependent autophagy in melanoma cells. Capsaicin treatment of mice implanted with melanoma cancer cells suppressed tumor growth by down-regulating tNOX and SIRT1, which was also seen in an in vivo xenograft study with tNOX-depleted melanoma cells. Conclusions: Together, our findings suggest that tNOX expression is important for the growth of melanoma cancer cells both in vitro and in vivo, and that inhibition of the tNOX-SIRT1 axis contributes to inducting cytotoxic ROS-dependent autophagy in melanoma cells.

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