Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent

Nasreddine, Ghenwa; El‐Sibai, Mirvat; Abi-Habib, Ralph J.

doi:10.1007/s10637-019-00756-w

Cited by 40 publications

(70 citation statements)

References 31 publications

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“…Our results indicated that autophagy was significantly induced after 8 h of BCA-M treatment in HeLa and SiHa cells with positive and negative ASS expressions, respectively ( Figure 8 ). The sign of autophagy induction after the treatment of BCA-M was similar to other reports with other types of arginine-depleting enzymes [ 18 , 46 , 47 ]. When autophagy is inhibited by CQ, the growth-inhibitory effect of BCA-M was enhanced synergistically ( Table 2 and Figure 9 ).…”

Section: Discussionsupporting

confidence: 90%

Recombinant Bacillus caldovelox Arginase Mutant (BCA-M) Induces Apoptosis, Autophagy, Cell Cycle Arrest and Growth Inhibition in Human Cervical Cancer Cells

Chung

Kim

Chow

et al. 2020

IJMS

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With our recent success in developing a recombinant human arginase drug against broad-spectrum cancer cell lines, we have explored the potential of a recombinant Bacillus caldovelox arginase mutant (BCA-M) for human cervical cancer treatment. Our studies demonstrated that BCA-M significantly inhibited the growth of human cervical cancer cells in vitro regardless of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) expression. Drug susceptibilities correlate well with the expressions of major urea cycle genes and completeness of L-arginine regeneration pathways. With the expressions of ASS and ASL genes conferring resistance to L-arginine deiminase (ADI) which is undergoing Phase III clinical trial, BCA-M offers the advantage of a broader spectrum of susceptible cancer cells. Mechanistic studies showed that BCA-M inhibited the growth of human cervical cancer cells by inducing apoptosis and cell cycle arrest at S and/or G2/M phases. Our results also displayed that autophagy served as a protective mechanism, while the growth inhibitory effects of BCA-M could be enhanced synergistically by its combination to the autophagy inhibitor, chloroquine (CQ), on human cervical cancer cells.

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Section: Discussionsupporting

confidence: 90%

Recombinant Bacillus caldovelox Arginase Mutant (BCA-M) Induces Apoptosis, Autophagy, Cell Cycle Arrest and Growth Inhibition in Human Cervical Cancer Cells

Chung

Kim

Chow

et al. 2020

IJMS

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“…This was followed by the addition of 50 µL HuArgI(Co)-PEG5000 in media to each well (Corning Inc. Corning, NY, USA) to yield concentrations ranging from 10 −7 to 10 −13 M. Following a 72-h incubation at 37 °C/5% CO 2 , 50 µL of XTT cell proliferation reagent (Roche, Basel, Switzerland) were added to each well and the plates incubated for 4 h. Absorbance was then read at 450 nm using a Varioskan Flash plate reader (Thermo Fisher Scientific, Waltham, MA, USA). Nominal absorbance and percent maximal absorbance were plotted against the log of concentration and a non-linear regression with a variable slope sigmoidal dose response curve was generated along with IC 50 using GraphPad Prism 5 software (GraphPad Software, San Diego, CA, USA) (as previously described [29,48]).…”

Section: Methodsmentioning

confidence: 99%

“…We and others have demonstrated the cytotoxicity and selectivity of [HuArgI (Co)-PEG5000]-induced arginine deprivation in a number of tumor types including acute lymphoid leukemia (ALL), hepatocellular carcinoma, glioblastoma multiorme (GBM), and acute myeloid leukemia (AML) [25,26,27,28,29]. The impact of [HuArgI (Co)-PEG5000]-induced arginine deprivation on tumor cell invasion and metastasis has recently been studied in gastric tumors and glioblastoma multiforme (GBM) [30,31].…”

Section: Introductionmentioning

confidence: 99%

Human Recombinant Arginase I [HuArgI (Co)-PEG5000]-Induced Arginine Depletion Inhibits Colorectal Cancer Cell Migration and Invasion

Al-Koussa

Haddad

Abi-Habib

et al. 2019

IJMS

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Purpose: Colorectal cancer (CRC) is the third most common type of cancer worldwide, and it represents over half of all gastrointestinal cancer deaths. Knowing that cancer cells have a high proliferation rate, they require high amounts of amino acids, including arginine. In addition, several tumor types have been shown to downregulate ASS-1 expression, becoming auxotrophic for arginine. Therefore, Arginine deprivation is one of the promising therapeutic approaches to target cancer cells. This can be achieved through the use of a recombinant human arginase, HuArgI(Co)-PEG5000, an arginine degrading enzyme. Methods: In this present study, the cytotoxic effect of HuArgI(Co)-PEG5000 on CRC cell lines (HT-29, Caco-2, Sw837) is examined though cytotoxicity assays. Wound healing assays, invasion assays, and adhesion assays were also performed to detect the effect on metastasis. Results: Wound healing and invasion assays revealed a decrease in cell migration and invasion after treatment with arginase. Cells that were treated with arginase also showed a decrease in adhesion, which coincided with a decrease in RhoA activation, demonstrated though the use of a FRET biosensor to detect RhoA activation in a single cell assay, and a decrease in MMP-9 expression. Treating cells with both arginase and L-citrulline, which significantly restores intracellular arginine levels, reversed the effect of HuArgI(Co)-PEG5000 on cell viability, migration, and invasion. Conclusion: We can, therefore, conclude that colorectal cancer is partially auxotrophic to arginine and that arginine depletion is a potential selective inhibitory approach for motility and invasion in colon cancer cells.

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“…The type of cell death was determined by ow cytometry using a modied protocol. 33,34 Briey, B16-F10 cells were treated with complex 1 (10 mM) and irradiated as described above or le in dark conditions. Aer 24 h incubation at 37 C/5% CO 2 , cells were harvested and treated for 5 min with PI (5 mg mL À1 ) and FITC-conjugated annexin V antibody (5 mg mL À1 ) at 37 C. Annexin V/PI data were then analyzed by ow cytometry on FL1-H versus FL2-H scatter plot.…”

Section: Analysis Of Cell Death By Ow Cytometrymentioning

confidence: 99%

Enhanced cellular uptake and photochemotherapeutic potential of a lipophilic strained Ru(ii) polypyridyl complex

et al. 2019

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Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent

Cited by 40 publications

References 31 publications

Recombinant Bacillus caldovelox Arginase Mutant (BCA-M) Induces Apoptosis, Autophagy, Cell Cycle Arrest and Growth Inhibition in Human Cervical Cancer Cells

Recombinant Bacillus caldovelox Arginase Mutant (BCA-M) Induces Apoptosis, Autophagy, Cell Cycle Arrest and Growth Inhibition in Human Cervical Cancer Cells

Human Recombinant Arginase I [HuArgI (Co)-PEG5000]-Induced Arginine Depletion Inhibits Colorectal Cancer Cell Migration and Invasion

Enhanced cellular uptake and photochemotherapeutic potential of a lipophilic strained Ru(ii) polypyridyl complex

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