Carbon monoxide sensitizes cisplatin-resistant ovarian cancer cell lines toward cisplatin via attenuation of levels of glutathione and nuclear metallothionein

Kawahara, Brian; Sivakumar, R; Chaudhuri, Gautam; Janzen, Carla; Sen, Suvajit; Mascharak, Pradip K.

doi:10.1016/j.jinorgbio.2018.11.003

Cited by 51 publications

(45 citation statements)

References 32 publications

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“…Furthermore, CO, generated by HO‐1, was reported to significantly increase the vascular permeability of solid tumors, which thus contributed to a selective accumulation of anticancer drugs in the tumor . Several CORMs have recently been shown to decrease chemotherapeutic resistance in various cancer cell types, such as ovarian cancer and breast cancer cells . At the same time, CORMs have also been utilized to overcome side effects caused by other anticancer therapy, such as doxorubicin‐induced cardiotoxicity, cisplatin‐induced nephrotoxicity as well as radiation‐induced bystander effect .…”

Section: The Application Of Co In Disease Therapymentioning

confidence: 99%

“…Recently, Gandra et al constructed a stable Mn(I) tricarbonyl complex with turn‐on fluorescence response upon release of CO, which has been utilized to track and confirm CO delivery in cellular matrices. Overall, the controlled release of CO from a few selected photoCORMs under light illumination was shown to play a beneficial therapeutic role in cancer and bacterial infection . But the limited tissue penetration depth of UV‐vis light accompanied by the presence of phototoxicity would confine the clinical application of photoCORMs.…”

Section: Carbon Monoxide Releasing Moleculesmentioning

confidence: 99%

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Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

Yan

Zhu

et al. 2019

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Carbon monoxide (CO) therapy has emerged as a hot topic under exploration in the field of gas therapy as it shows the promise of treating various diseases. Due to the gaseous property and the high affinity for human hemoglobin, the main challenges of administrating medicinal CO are the lack of target selectivity as well as the toxic profile at relatively high concentrations. Although abundant CO releasing molecules (CORMs) with the capacity to deliver CO in biological systems have been developed, several disadvantages related to CORMs, including random diffusion, poor solubility, potential toxicity, and lack of on‐demand CO release in deep tissue, still confine their practical use. Recently, the advent of versatile nanomedicine has provided a promising chance for improving the properties of naked CORMs and simultaneously realizing the therapeutic applications of CO. This review presents a brief summarization of the emerging delivery strategies of CO based on nanomaterials for therapeutic application. First, an introduction covering the therapeutic roles of CO and several frequently used CORMs is provided. Then, recent advancements in the synthesis and application of versatile CO releasing nanomaterials are elaborated. Finally, the current challenges and future directions of these important delivery strategies are proposed.

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Section: The Application Of Co In Disease Therapymentioning

confidence: 99%

Section: Carbon Monoxide Releasing Moleculesmentioning

confidence: 99%

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

Yan

Zhu

et al. 2019

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101

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“…Multidrug resistance is the main barrier against successful cancer chemotherapy. Several mechanisms and pathways are involved in MDR development, but the main mechanism for resistance to cisplatin is enhanced drug inactivation by cellular GSH (Kawahara et al, ; Meijer et al, ; Nikounezhad et al, ; Perez, ). GSH, an important intracellular antioxidant defense, conjugates to active electrophilic cisplatin inside the cells and inactivates it before reaching to DNA.…”

Section: Discussionmentioning

confidence: 99%

“…They found that reduction in GSH levels sensitized colonic cancer cells to cisplatin (Iida et al, ). In a very recent study performed by Kawahara and colleagues, targeting an enzyme involved in sulfur metabolism (cystathionine β‐synthase), by exogenous carbon monoxide (CO) enhanced the sensitivity of ovarian cancer cells to cisplatin through intracellular GSH reduction (Kawahara et al, ). Therefore, targeting intracellular GSH can be a promising approach to overcome cisplatin resistance.…”

Section: Discussionmentioning

confidence: 99%

Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin‐resistant ovarian cancer (A2780) cells

et al. 2019

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Ovarian cancer is considered as one of the most lethal gynecological cancers, and cisplatin-based therapy has an important role as the first-line option for chemotherapy.Resistance to chemotherapy is the main obstacle against successful cancer chemotherapy with cisplatin. Therefore, identifying potent compositions and molecules with fewer side-effects is a big challenge to overcome cisplatin resistance. In this study, we investigated the possible mechanism and potency of sanguinarine, a plantderived alkaloid, in human cisplatin-resistant ovarian cancer (A2780/R) cells. The effect of sanguinarine on cytotoxicity of cisplatin was determined by MTT assay.Apoptosis-inducing effect of sanguinarine alone and in combination with cisplatin was evaluated by annexin V/PI assay and DAPI staining. Intracellular glutathione (GSH) content was quantitated using GSH assay kit after treatment with sanguinarine. Results indicated that sanguinarine enhances the sensitivity of A2780/R cells to cisplatin. Apoptosis-inducing effect of cisplatin was also enhanced when combined with sanguinarine. Furthermore, sanguinarine reduced intracellular GSH content in a dose-dependent but not time-dependent manner. These findings suggest that sanguinarine could reverse cisplatin resistance in A2780/R cells through GSH reduction.Therefore, sanguinarine can be used as one of the potent adjuvants for ovarian cancer chemotherapy. K E Y W O R D Scisplatin resistance, glutathione, ovarian cancer, sanguinarine

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“…2 The challenge of delivering efficacious concentrations of CO to a target tissue has been approached by our group and others by synthesizing CO-releasing molecules (CORMs) with properties necessary for a potential therapeutic, including water solubility, 3 incorporation within biocompatible materials 4,5 and controllable release of CO. [6][7][8][9] Very recently, with the use of photoactivatable CORMs (photoCORMs) our group has elucidated mechanism(s) by which CO exerts deleterious effects against human breast and ovarian cancer cell models. 10,11 In such studies we have observed sensitization of ovarian cancer cells to drugs like cisplatin and paclitaxel through coadministration of CO. 11 Because sensitization to conventional chemotherapeutics could mitigate the poor outcome of ovarian cancer treatment, precise target-specic delivery of CO to the malignant tissue appears to be a very desirable goal.…”

Section: Introductionmentioning

confidence: 99%

Diminished viability of human ovarian cancer cells by antigen-specific delivery of carbon monoxide with a family of photoactivatable antibody-photoCORM conjugates

et al. 2020

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Carbon monoxide (CO)-releasing antibody conjugates were synthesized utilizing a photoactivatable COreleasing molecule (photoCORM) and mouse monoclonal antibodies linked by a biotin-streptavidin system. Different monoclonal antibodies raised against different surface-expressed antigens that are implicated in ovarian cancer afforded a family of antibody-photoCORM conjugates (Ab-photoCORMs). In an immunosorbent/cell viability assay, Ab-photoCORMs accumulated onto ovarian cancer cells expressing the target antigens, delivering cytotoxic doses of CO in vitro. The results described here provide the first example of an "immunoCORM", a proof-of-the-concept antibody-drug conjugate that delivers a gaseous molecule as a warhead to ovarian cancer. † Electronic supplementary information (ESI) available: Synthetic scheme and calculations for CO release (Schemes S1 and S2). Spectroscopic, chromatography and mass spectrometry data ( Fig. S1-S4, S8 and S9). Myoglobin assays and cell toxicity/viability data (Fig. S5-S7 and S10-S13). Description of the experimental procedures. See Scheme 1 Live-cell, immunosorbent assay scheme utilized for assessment of the efficacy of antigen-recognition of an antibody-(photoactivated carbon monoxide-releasing molecule) conjugate (Ab-photoCORM) to deliver cytotoxic levels of carbon monoxide to ovarian cancer cells compared to a non-specific Ab-photoCORM conjugate.This journal is

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Carbon monoxide sensitizes cisplatin-resistant ovarian cancer cell lines toward cisplatin via attenuation of levels of glutathione and nuclear metallothionein

Cited by 51 publications

References 32 publications

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin‐resistant ovarian cancer (A2780) cells

Diminished viability of human ovarian cancer cells by antigen-specific delivery of carbon monoxide with a family of photoactivatable antibody-photoCORM conjugates

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