Inhibitory Growth of Oral Squamous Cell Carcinoma Cancer via Bacterial Prodigiosin

Cheng, Ming‐Fang; Lin, Chun–Shu; Chen, Yu‐Hsin; Sung, Ping‐Jyun; Lin, Shian-Ren; Tong, Yi-Wen; Weng, Ching‐Feng

doi:10.3390/md15070224

Cited by 38 publications

(35 citation statements)

References 67 publications

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“…PG could activate autophagy of OSCC cells as proven by the previous section and literature [ 48 ]. In this final part, the aim was to find the trigger of PG-induced autophagy in OSCC cells.…”

Section: Resultsmentioning

confidence: 63%

“…Cytotoxicity was determined using a colorimetric assay by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) previously described in the literature [ 48 ]. The optical density (OD) alteration of mitochondrial enzymatic activity was converted into the cell numbers according to the cell viability or cytotoxicity.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, PG showed apoptotic inducing property in many cancer types such as lung cancer [ 35 , 36 , 37 ], breast cancer [ 38 , 39 ], colorectal cancer [ 40 , 41 , 42 ], leukemia [ 43 , 44 ], and hepatocellular carcinoma [ 45 ] without normal cell cytotoxicity [ 41 , 46 ]. Recently, PG has also been identified as an autophagy inducer in OSCC cells [ 47 , 48 ]. However, the application of PG as an adjuvant in chemotherapy is still unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Lin

Weng

2018

JCM

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Synergistic effects between natural compounds and chemotherapy drugs are believed to have fewer side effects with equivalent efficacy. However, the synergistic potential of prodigiosin (PG) with doxorubicin (Dox) chemotherapy is still unknown. This study explores the synergistic mechanism of PG and Dox against oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines were treated with different PG/Dox combinatory schemes for cytotoxicity tests and were further investigated for cell death characteristics by cell cycle flow cytometry and autophagy/apoptosis marker labelling. When OSCC cells were pretreated with PG, the cytotoxicity of the subsequent Dox-treatment was 30% higher than Dox alone. The cytotoxic efficacy of PG-pretreated was found better than those of PG plus Dox co-treatment and Dox-pretreatment. Increase of Sub-G1 phase and caspase-3/LC-3 levels without poly (ADP-ribose) polymeras (PARP) elevation indicated both autophagy and necrosis occurred in OSCC cells. Dox flux after PG-priming was further evaluated by rhodamine-123 accumulation and Dox transporters analysis to elucidate the PG-priming effect. PG-priming autophagy enhanced Dox accumulation according to the increase of rhodamine-123 accumulation without the alterations of Dox transporters. Additionally, the cause of PG-triggered autophagy was determined by co-treatment with endoplasmic reticulum (ER) stress or AMP-activated protein kinase (AMPK) inhibitor. PG-induced autophagy was not related to nutrient deprivation and ER stress was proved by co-treatment with specific inhibitor. Taken together, PG-priming autophagy could sensitize OSCC cells by promoting Dox influx without regulation of Dox transporter. The PG-priming might be a promising adjuvant approach for the chemotherapy of OSCC.

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Section: Resultsmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lin

Weng

2018

JCM

Self Cite

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“…Prodigiosin, 2-methyl-3-pentyl-6-methoxyprodiginine, is thought to contribute to bacterial competition, and has antitumor capabilities [37,40,41]. Furthermore, prodigiosin was recently shown to activate autophagic cell death in a variety of cancer cell lines and to reduce tumor proliferation in mouse tracheas [42][43][44][45][46][47][48][49]. Many clinical isolates of S. marcescens do not synthesize prodigiosin [50], and perhaps this benefits them by reducing activation of the host's innate immune response.…”

Section: Discussionmentioning

confidence: 99%

Biologically active pigment and ShlA cytolysin of Serratia marcescens induce autophagy in a human ocular surface cell line

Stella

Shanks

2020

BMC Ophthalmol

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Background: The cellular process of autophagy is essential for maintaining the health of ocular tissue. Dysregulation of autophagy is associated with several ocular diseases including keratoconus and macular degeneration. It is known that autophagy can be used to respond to microbial infections and that certain microbes can exploit the autophagic process to their benefit. In this study, a genetic approach was used to identify surfaceassociated and secreted products generated by the opportunistic pathogen Serratia marcescens involved in activation of autophagy. Methods: A recombinant human corneal limbal epithelial cell line expressing a LC3-GFP fusion protein was challenged with normalized secretomes from wild-type and mutant S. marcescens derivatives. LC3-GFP fluorescence patterns were used to assess the ability of wild-type and mutant bacteria to influence autophagy. Purified prodigiosin was obtained from stationary phase bacteria and used to challenge ocular cells. Results: Mutations in the global regulators eepR and gumB genes highly reduced the ability of the bacteria to activate autophagy in corneal cells. This effect was further narrowed down to the secreted cytolysin ShlA and the biologically active pigment prodigiosin. Purified prodigiosin and ShlA from Escherichia coli further supported the role of these factors in activating autophagy in human corneal cells. Additional genetic data indicate a role for flagellin and type I pili, but not the nuclease, S-layer protein, or serratamolide biosurfactant in activation of autophagy. Conclusions: This work identifies specific bacterial components that activate autophagy and give insight into potential host-pathogen interactions or compounds that can be used to therapeutically manipulate autophagy.

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“…From WB and immunofluorescence analysis 45 was able to activate the AMPKα, PI3K/Akt signaling pathway and to inhibit mTOR. Also, it was able to reduce the levels of beclin‐1 and to increase the expression of p62 and LC3‐II determining, in this way, autophagic cell death . The synergistic effects between the association of AZD2014 ( 20a ) and radiation were evaluated in a work by Yu et al This compound reduced the cell viability by 63% after 48 hours at a concentration of 100 nM against SCC25 (tongue squamous cell carcinoma) cells.…”

Section: Autophagy Modulators In Oscc and Esccmentioning

confidence: 99%

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Khan

Relitti

Brindisi

et al. 2019

Medicinal Research Reviews

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Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC.Additionally, we provide a viewpoint on the state of the art Tuhina Khan and Nicola Relitti contributed equally to this work. and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC. K E Y W O R D S autophagy, autophagy modulators, biomarkers, esophageal squamous cell carcinoma, exosomes, oral squamous cell carcinoma, targeted therapy 1 | INTRODUCTION Oral squamous cell carcinoma (OSCC) is the predominant malignant neoplasm of the oral cavity followed by verrucous carcinoma, undifferentiated carcinoma, and small salivary adenocarcinoma. 1 Esophageal squamous cell carcinoma (ESCC) is the first histological type and accounts for 80% of cases of esophageal cancer. 2 OSCC and ESCC are indicated as one of the most common cancers by the International Union Against Cancer with an annual incidence of 275 000 and 456 000 cases worldwide, respectively. 3,4 The primary etiology in both OSCC and ESCC is attributed to the environmental factors (tobacco abuse, alcohol consumption), genetic factors (eg, mutations in enzymes), viral factors (human papilloma virus [HPV] infection), and/or the coexistence of these factors. Alcohol intake and tobacco use are responsible for at least 75% of these carcinomas. The underlying initiation and progression mechanisms of OSCC and ESCC are generally characterized by the accumulation of serial epigenetic and genetic alterations, which eventually lead to uncontrolled proliferation of the mutated cells, followed by vigorous cell division. 5,7 Early-stage OSCC detection displays an 80% survival rate at 5 years, while detection at advanced stage leads to survival rates ranging from 20% to 40%. 6 In ESCC, the 5-year survival rate for early-stage detection may reach 85%, whereas a dr...

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Inhibitory Growth of Oral Squamous Cell Carcinoma Cancer via Bacterial Prodigiosin

Cited by 38 publications

References 67 publications

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

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

Biologically active pigment and ShlA cytolysin of Serratia marcescens induce autophagy in a human ocular surface cell line

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

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