PG-Priming Enhances Doxorubicin Influx to Trigger Necrotic and Autophagic Cell Death in Oral Squamous Cell Carcinoma

Lin, Shian-Ren; Weng, Ching‐Feng

doi:10.3390/jcm7100375

Cited by 18 publications

(22 citation statements)

References 78 publications

(92 reference statements)

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“…This interesting phenomenon hinders physiological polymorphism of commercial cell lines in cellular levels. Previously, similar phenomenon could be found in prodigiosin (PG)/Dox synergistic study in OSCC cells, and PG against NSCLC cells 15,24 . However, the discussion of this phenomenon was rare.…”

Section: Discussionsupporting

confidence: 70%

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Chiu¹,

Shen²,

Wu³

et al. 2020

Preprint

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Background: The antitumor activity of HCD has been reported in numerous types of cancers. Moreover, the antitumor of HCD could also be applied in non-small-cell lung cancer (NSCLC) cells and further act on doxorubicin-resistant (Dox-R) of NSCLC cells. The underlying anti-cancer mechanism of HCD on Dox-R versus Dox-sensitive (Dox-S) of A549 cells was under this investigation. Methods: Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot; and further examination of its anti-cancer efficacy in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation. Result: Regardless sensitive and resistant to Dox, HCD could arrest both Dox-S and Dox-R cells at G 2 /M phase without altering the sub-G 1 cycle along with increasing cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI 3 K-ClassIII/Beclin-1 and upregulated p62/LC3-I/II expressions, further confirmed the cell autophagy after HCD-induced. Morphological observations of the mouse lung sections illustrated that fewer cancer cells accumulated around the trachea while there were less neoplastic activities found in HCD orthotopic treatment mice without liver, kidney and spleen toxicity. Conclusion: HCD exhibited the chemotherapeutic potential for lung cancer in Dox-resistant cells, suggesting natural autophagic inducer HCD provides a promising clue of new drug discovery and development for lung cancer therapy.

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Section: Discussionsupporting

confidence: 70%

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Chiu¹,

Shen²,

Wu³

et al. 2020

Preprint

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“…Cytotoxicity analysis was performed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) staining with viable cells as described in a previous study [19]. Briefly, 1 × 10 4 cells/well of normal cells were inoculated into 96-well plate and incubated under cultural conditions overnight.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

“…Cell cycle of treated cells was measured by propidium iodide (PI)-staining and flow cytometry according to the literature [19]. 1 × 10 6 cells/well of normal cells were seeded into 6-well plate.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

“…A Dox influx assay was performed by the accumulation of Dox-transporter substrate rhodamine 123 (R123) in the literature [19]. 1 × 10 4 cells/well of normal cells were inoculated into a 96-well plate.…”

Section: Dox Influx Assaymentioning

confidence: 99%

“…Accordingly, additional agents for enhancing the efficacy of adjuvant chemotherapeutic drugs or extending patient polymorphism need to developed using this new strategy. Previously, Dox accumulation caused by prodigiosin (PG)-priming has been confirmed in OSCC through the elevation of Dox influx [19]. However, the caused damage of PG/Dox combination in known organs, e.g., liver, kidney, and heart were not assessed.…”

Section: Introductionmentioning

confidence: 99%

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Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells

Lin

Chen

et al. 2020

Mol Cell Biochem

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Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox’s cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox’s effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

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Bacterial pigments: A colorful palette reservoir for biotechnological applications

Orlandi

Martegani

Giaroni

et al. 2021

Biotech and App Biochem

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Synthetic derivatives are currently used instead of pigments in many applicative fields, from food to feed, from pharmaceutical to diagnostic, from agronomy to industry. Progress in organic chemistry allowed to obtain rather cheap compounds covering the whole color spectrum. However, several concerns arise from this chemical approach, as it is mainly based on nonrenewable resources such as fossil oil, and the toxicity or carcinogenic properties of products and/or precursors may be harmful for personnel involved in the productive processes. In this scenario, microorganisms and their pigments represent a colorful world to discover and reconsider. Each living bacterial strain may be a source of secondary metabolites with peculiar functions. The aim of this review is to link the physiological role of bacterial pigments with their potential use in different biotechnological fields. This enormous potential supports the big challenge for the development of strategies useful to identify, produce, and purify the right pigment for the desired application. At the end of this ideal journey through the world of bacterial pigments, the attention will be focused on melanin compounds, whose production relies upon different techniques ranging from natural producers, heterologous hosts, or isolated enzymes. In a green workflow, the microorganisms represent the starting and final point of pigment production.

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PG-Priming Enhances Doxorubicin Influx to Trigger Necrotic and Autophagic Cell Death in Oral Squamous Cell Carcinoma

Cited by 18 publications

References 78 publications

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells

Bacterial pigments: A colorful palette reservoir for biotechnological applications

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