Methionine Gamma Lyase from Clostridium sporogenes Increases the Anticancer Efficacy of Doxorubicin on A549 Cancer Cells In Vitro and Human Cancer Xenografts

Pokrovsky, Vadim S.; Anisimova, Natalia; Давыдов, Д Ж; Bazhenov, Sergey V.; Bulushova, N. V.; Zavilgelsky, G. B.; Kotova, V. Yu.; Манухов, И. В.

doi:10.1007/978-1-4939-8796-2_18

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…As with other therapies, the adaptation of bacterialbased treatments to specific cancer types, tumour sizes, and individual patient characteristics is likely to be crucial. Clostridium species have demonstrated tumour shrinkage across various cancers, including mammary/breast cancer (mouse model) (Abedi Jafari et al, 2022;Minton et al, 1995), Ehrlich carcinoma (mouse model) (Möse & Möse, 1964), sarcoma (mouse model), melanoma (hamster model) (Thiele et al, 1964), colon carcinoma (mouse model) (Dang et al, 2001;Diaz et al, 2005;Heap et al, 2014), lung carcinoma (mouse model) (Mowday et al, 2022;Pokrovsky et al, 2019), glioblastoma (mouse model) (V. Staedtke et al, 2022), glioblastoma (rat model) (Verena Staedtke et al, 2015), pancreatic cancer (mouse model) (Zheng et al, 2015), sarcoma (dog study) (Roberts et al, 2014), retroperitoneal leiomyosarcoma (human patient) (Roberts et al, 2014), and solid tumours in human patients (Janku et al, 2021). While oncolysis has been achieved with Clostridium injections alone (either intravenous or intratumoral), combination therapies incorporating bacteria with other agents have shown greater success in achieving complete tumour destruction.…”

Section: Discussionmentioning

confidence: 99%

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Using spore-forming bacteria to treat cancer: recent advancements in clostridial-based therapies

Rodrigues¹

2023

SciRevs.Biology

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The use of bacteria in cancer therapy has emerged as a promising approach, offering unique advantages for targeted treatment and immunotherapy. This review paper explores some recent advances in the application of bacteria, particularly Clostridium species, in cancer therapy. For instance, the Clostridial-Directed Enzyme Prodrug Therapy (CDEPT) utilises non-pathogenic strains of Clostridium as carriers for targeted delivery of anti-cancer drugs to solid tumour cells. This strategy aims to minimise systemic side effects associated with traditional chemotherapy. Additionally, Clostridium novyi and Clostridium sporogenes present oncolytic properties and have shown potential for tumour regression in preclinical models. The engineering of these bacteria to produce cytokines, such as interleukin-12 (IL-12) and interleukin-2 (IL-2), further enhances their therapeutic potential by activating the immune system to target cancer cells. Clinical trials in humans have demonstrated the feasibility and safety of C. novyi-based therapies, and early results indicate potential efficacy in tumour regression. Overall, this review provides valuable insights into the multifaceted roles of bacteria, particularly Clostridium species, in cancer therapy, emphasizing their potential as targeted therapeutics and immunomodulators for improved cancer treatment outcomes.

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Section: Discussionmentioning

confidence: 99%

“…Subsequent testing of MGL, both as a standalone treatment and in combination with another compound, involved A549 human lung cancer cells. Encouragingly, when combined with doxorubicin (DOX), MGL demonstrated cytotoxicity and exhibited tumour growth inhibition (Pokrovsky et al, 2019).…”

Section: Clostridium Sporogenes As a Versatile Tool For Targeted Canc...mentioning

confidence: 99%

Using spore-forming bacteria to treat cancer: recent advancements in clostridial-based therapies

Rodrigues¹

2023

SciRevs.Biology

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“…The enzymes commonly utilized in EPT are non-mammalian or have low systemic abundance in the organism [ 13 ]. Since the 1980s, MGLs from different sources have been evaluated as anticancer agents [ 14 , 15 ]. The absence of MGL in mammals makes the enzyme a suitable candidate for EPT.…”

Section: Discussionmentioning

confidence: 99%

Methionine γ-Lyase-Daidzein in Combination with S-Propyl-L-cysteine Sulfoxide as a Targeted Prodrug Enzyme System for Malignant Solid Tumor Xenografts

Qoura

Morozova

Kulikova

et al. 2022

IJMS

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The purpose of this study was to determine the anticancer effect of dipropyl thiosulfinate produced in situ by the pharmacological pair: (1) conjugated with daidzein C115H methionine γ-lyase (EC 4.4.1.11, C115H MGL-Dz) and (2) the substrate, S-propyl-L-cysteine sulfoxide (propiin) against various solid tumor types in vitro and in vivo. The MTT test was used to calculate IC50 values for HT29, COLO205 and HCT116 (colon cancer); Panc1 and MIA-PaCa2 (pancreatic cancer); and 22Rv1, DU-145 and PC3 (prostate cancer). The most promising effect for colon cancer cells in vitro was observed in HT29 (IC50 = 6.9 µM). The IC50 values for MIA-PaCa2 and Panc1 were 3.4 and 3.8 µM, respectively. Among prostate cancer cells, 22Rv1 was the most sensitive (IC50 = 5.4 µM). In vivo antitumor activity of the pharmacological pair was studied in HT29, SW620, Panc1, MIA-PaCa2 and 22Rv1 subcutaneous xenografts in BALB/c nude mice. The application of C115H MGL-Dz /propiin demonstrated a significant reduction in the tumor volume of Panc1 (TGI 67%; p = 0.004), MIA-PaCa2 (TGI 50%; p = 0.011), HT29 (TGI 51%; p = 0.04) and 22Rv1 (TGI 70%; p = 0.043) xenografts. The results suggest that the combination of C115H MGL-Dz/propiin is able to suppress tumor growth in vitro and in vivo and the use of this pharmacological pair can be considered as a new strategy for the treatment of solid tumors.

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Obligate and facultative anaerobic bacteria in targeted cancer therapy: Current strategies and clinical applications

Dróżdż¹,

Makuch

Cieniuch³

et al. 2020

Life Sciences

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Methionine Gamma Lyase from Clostridium sporogenes Increases the Anticancer Efficacy of Doxorubicin on A549 Cancer Cells In Vitro and Human Cancer Xenografts

Cited by 4 publications

References 22 publications

Using spore-forming bacteria to treat cancer: recent advancements in clostridial-based therapies

Using spore-forming bacteria to treat cancer: recent advancements in clostridial-based therapies

Methionine γ-Lyase-Daidzein in Combination with S-Propyl-L-cysteine Sulfoxide as a Targeted Prodrug Enzyme System for Malignant Solid Tumor Xenografts

Obligate and facultative anaerobic bacteria in targeted cancer therapy: Current strategies and clinical applications

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