Fraction B From Catfish Epidermal Secretions Kills Pancreatic Cancer Cells, Inhibits CD44 Expression and Stemness, and Alters Cancer Cell Metabolism

Al-Hassan, Jassim M.; Wei, Daoyan; Chakraborty, Sharmistha; Conway, Tara; Rhea, Patrea R.; Wei, Bo; Tran, Megan; Gagea, Mihai; Afzal, Muhammad; Oommen, Sosamma; Nair, Divya; Paul, Bincy M.; Yang, Peiying

doi:10.3389/fphar.2021.659590

Cited by 3 publications

(3 citation statements)

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“…No deformity or gross pathological alterations in all the organs were detected at the end of the experiment. These findings agree with our recent in vivo and in vitro studies that showed Fraction B has no toxic effect on the blood cells of the treated animals ( Al-Hassan et al, 2021 ). In another study, normal healthy animals were treated daily with FB (IP) for 4 months, grew well, and on dissection, showed no physical abnormalities (data not shown).…”

Section: Resultssupporting

confidence: 93%

“…Recent results at MD Anderson Cancer Center in Houston, TX, have demonstrated that different lipid-soluble fractions separated from catfish skin preparations (CSP) have anti-inflammatory and anti-proliferative effects against prostate, pancreatic, lung, skin, and liver cancer cell lines ( Yang et al, 2016 ; Al-Hassan et al, 2019 ; Al-Hassan et al, 2021 ). Our collaborators at Sick Children Hospital Research Institute, Toronto, have established that lipid fractions and pure lipid components from skin secretions have high activity against leukemia K562 synergistically with Gleevec ( Al-Hassan et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Our collaborators at Sick Children Hospital Research Institute, Toronto, have established that lipid fractions and pure lipid components from skin secretions have high activity against leukemia K562 synergistically with Gleevec ( Al-Hassan et al, 2020 ). In addition, recently, we proved that Fraction B has a potent effect against human (Panc-1) and mouse (Panc-02) pancreatic cancer cells ( Al-Hassan et al, 2019 ) and breast MDA MB-231 and leukemic K-562 cancer cell lines in a dose-dependent fashion ( Al-Hassan et al, 2021 ). FB treatment also accelerated wound healing created by a transdermal punch biopsy of the rat skin ( Al-Hassan et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Neuroregeneration of injured peripheral nerve by fraction B of catfish epidermal secretions through the reversal of the apoptotic pathway and DNA damage

2023

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Introduction: Crush injuries occur from acute traumatic nerve compression resulting in different degrees of neural damage leading to permanent functional deficits. Recently, we have shown that administration of Fraction B (FB) derived from catfish epidermal secretions accelerates healing of damaged nerve in a sciatic nerve crush injury, as it ameliorates the neurobehavioral deficits and enhances axonal regeneration, as well as protects spinal neurons and increases astrocytic activity and decreasing GAP-43 expression. The present study aimed to investigate the role of FB treatment on the apoptotic pathway in the neuroregeneration of the sciatic nerve crush injury.Methods: Male Wistar rats were randomly assigned into five groups: (I) SHAM, (II) CRUSH, (III) CRUSH + (1.5 mg/kg) FB, (IV) CRUSH + (3 mg/kg) FB, and (V) CRUSH + (4.5 mg/kg) FB. Rats underwent sciatic nerve crush surgery, followed by treatment with FB administered intraperitoneally (IP) daily for two weeks and then sacrificed at the end of the fourth week.Results: FB improved the recovery of neurobehavioral functions with a concomitant increase in axonal regeneration and neuroprotective effects on spinal cord neurons following crush injury. Further, FB enhanced Schwann cells (SCs) proliferation with a significant increase in myelin basic protein expression. FB-treated animals demonstrated higher numbers of neurons in the spinal cord, possibly through ameliorating oxidative DNA damage and alleviating the mitochondrial-dependent apoptotic pathway by inhibiting the release of cytochrome c and the activation of caspase-3 in the spinal cord neurons.Conclusion: FB alleviates the neurodegenerative changes in the lumbar spinal cord neurons and recovers the decrease in the neuronal count through its anti-apoptotic and DNA antioxidative properties.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuroregeneration of injured peripheral nerve by fraction B of catfish epidermal secretions through the reversal of the apoptotic pathway and DNA damage

2023

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Targeting Glutamine Metabolism with a Novel Na+/K+-ATPase Inhibitor RX108 in Hepatocellular Carcinoma

Wei

Chen

Mou³

et al. 2023

Molecular Cancer Therapeutics

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The poor prognosis and limited therapeutic options for human hepatocellular carcinoma (HCC), the most common form of liver cancer, highlight the urgent need to identify novel therapeutic modalities. Here we describe the antitumor activity and underlying molecular mechanisms of a novel Na+/K+-ATPase inhibitor RX108 in human HCC cells and its xenograft model. RX108 dose-dependently inhibited HCC cell proliferation in vitro and tumor growth in a xenograft mouse model, and that the inhibition was associated with induction of apoptosis. Mechanistically, RX108 significantly downregulated alanine serine cysteine transporter 2 (ASCT2) protein expression and reduced glutamine and glutamate concentration in HCC cells and tumors. Additionally, RX108 exposure led to a significant decrease in cell energy metabolism in Huh7 and Hep3B cells, including decreased levels of glutathione, NADH, NADPH, and mitochondrial respiration oxygen consumption rate (OCR). Furthermore, HCC cells exhibited evidence of glutamine addiction; the antiproliferative effect of RX108 was dependent on glutamine transport. Clinically, elevated ASCT2 mRNA expression in HCCs was associated with unfavorable survival. Taken together, these findings reveal a novel approach to target glutamine metabolism through inhibiting Na+/K+-ATPase and provide a rationale for using RX108 to treat HCC in patients whose tumors express ASCT2 at high levels. RX108 is currently under clinical development.

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Oxysterols in catfish skin secretions (Arius bilineatus, Val.) exhibit anti-cancer properties

et al. 2022

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The edible catfish Arius bilineatus, (Valenciennes) elaborates a proteinaceous gel-like material through its epidermis when threatened or injured. Our on-going studies on this gel have shown it to be a complex mixture of several biologically active molecules. Anti-cancer studies on lipid fractions isolated from the gel-like materials showed them to be active against several cancer cell lines. This prompted us to investigate further the lipid composition of the catfish epidermal gel secretions (EGS). Analysis of the lipid fraction of EGS resulted in identification of 12 oxysterols including cholesterol and 2 deoxygenated steroids i.e., 7α-hydroxy cholesterol, 7β-hydroxycholesterol, 5,6 epoxycholesterol, 3β-hydroxycholest-5-ene-7-one and cholesta-3,5-dien-7-one. Progesterone, cholest-3,5-diene, cholesta-2,4-diene, cholest-3,5,6-triol and 4-cholesten-3-one were found as minor components, and were identified through their MS, 1HNMR and FTIR spectral data and were compared with those of the standards. Cholest-3,6-dione, cholesta-4,6-diene-3-one, cholesta-2,4-diene, and cholesta-5,20(22)-dien-3-ol were found only in trace amounts and were identified by GC/MS/MS spectral data. Since cholesterol is the major component of EGS, the identified oxysterols (OS) are presumably cholesterol oxidation products. Many of the identified OS are known important biological molecules that play vital physiological role in the producer and recipient organisms. We report herein the effects of these sterols on three human cancer cell lines in vitro, i.e., K-562 (CML cell line), MDA MB-231 (estrogen positive breast cancer cell line) and MCF-7 (estrogen negative breast cancer cell line). Interestingly significant (p < 0.05) dose differences were observed between tested OS on cell types used. The presence of these sterols in EGS may help explain some aspects of the physiological activities of fraction B (FB) prepared from EGS, such as enhanced wound and diabetic ulcer healing, anti-inflammatory action and cytotoxic activities reported in our previous studies. The anti-proliferative actions of some of these oxysterols especially the cholesterol 3,5,6-triol (#5) as established on selected cancer cell lines in this study support our previous studies and make them candidates for research for human application.

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Fraction B From Catfish Epidermal Secretions Kills Pancreatic Cancer Cells, Inhibits CD44 Expression and Stemness, and Alters Cancer Cell Metabolism

Cited by 3 publications

References 47 publications

Neuroregeneration of injured peripheral nerve by fraction B of catfish epidermal secretions through the reversal of the apoptotic pathway and DNA damage

Neuroregeneration of injured peripheral nerve by fraction B of catfish epidermal secretions through the reversal of the apoptotic pathway and DNA damage

Targeting Glutamine Metabolism with a Novel Na+/K+-ATPase Inhibitor RX108 in Hepatocellular Carcinoma

Oxysterols in catfish skin secretions (Arius bilineatus, Val.) exhibit anti-cancer properties

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