PARP inhibitor Olaparib Enhances the Apoptotic Potentiality of Curcumin by Increasing the DNA Damage in Oral Cancer Cells through Inhibition of BER Cascade

Molla, Sefinew; Hembram, Krushna Chandra; Chatterjee, Subhajit; Nayak, Deepika; Sethy, Chinmayee; Pradhan, Rajalaxmi; Kundu, Chanakya Nath

doi:10.1007/s12253-019-00768-0

Cited by 21 publications

(12 citation statements)

References 36 publications

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“…TMZ is a DNA alkylating agent which is used for treating several malignancies, including GBM and SCLC with brain metastasis [18] , [38] . TMZ-mediated DNA damage is repaired by the BER pathway, for which PARP enzymes are required [21] .…”

Section: Discussionmentioning

confidence: 99%

“…In clinical applications, PARP inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, have demonstrated sustained anti-tumor responses as single agents in patients with BRCA1- or BRCA2-mutations [13] , [14] , [15] , [16] , [17] . PARP inhibitors can potentiate efficacy of genotoxic agents such as DNA alkylating agents, by disruption of BER in the DNA repair pathway [18] . Thus, another direction for PARP inhibitors in clinical development is their combination with chemotherapies [15] .…”

Section: Introductionmentioning

confidence: 99%

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Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor

et al. 2020

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Pamiparib, an investigational Poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development, demonstrates excellent selectivity for both PARP1 and PARP2, and superb anti-proliferation activities in tumor cell lines with BRCA1/2 mutations or HR pathway deficiency (HRD). Pamiparib has good bioavailability and is 16-fold more potent than olaparib in an efficacy study using BRCA1 mutated MDA-MB-436 breast cancer xenograft model. Pamiparib also shows strong anti-tumor synergy with temozolomide (TMZ), a DNA alkylating agent used to treat brain tumors. Compared to other PARP inhibitors, pamiparib demonstrated improved penetration across the blood brain barrier (BBB) in mice. Oral administration of pamiparib at a dose as low as 3 mg/kg is sufficient to abrogate PARylation in brain tumor tissues. In SCLC-derived, TMZ-resistant H209 intracranial xenograft model, combination of pamiparib with TMZ overcomes its resistance and shows significant tumor inhibitory effects and prolonged life span. Our data suggests that combination of pamiparib with TMZ has unique potential for treatment of brain tumors. Currently, the combination therapy of pamiparib with TMZ is evaluated in clinical trial [NCT03150862].

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor

et al. 2020

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“…Further reduction of luciferase activity and base excision repair (BER) expression and PARylation suggest the promising efficiency of curcumin and olaparib in combination to inhibit BER activity in the oral cells. In vivo study of curcumin with olaparib showed a similar outcome with the decreased tumor growth and induction of apoptosis and improvement in body weight of tumor mice …”

Section: Oral Cancermentioning

confidence: 67%

“…In vivo study of curcumin with olaparib showed a similar outcome with the decreased tumor growth and induction of apoptosis and improvement in body weight of tumor mice. 238 Curcumin treatment in the range of 0−50 μM dose dependently inhibited the cancer cell proliferation, stemness, and expression of miRNA-21 in human papillomavirus (HPV)+ve/HPV-ve oral cancer cells. Furthermore, the effect was more prominent in the case of HPV-positive cancer stem cells (CSCs) as compared with the other cancer cells.…”

Section: ■ Gingivitismentioning

confidence: 99%

From Simple Mouth Cavities to Complex Oral Mucosal Disorders—Curcuminoids as a Promising Therapeutic Approach

Girisa

Kumar

Rana

et al. 2021

ACS Pharmacol. Transl. Sci.

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Oral diseases are among the most common encountered health issues worldwide, which are usually associated with anomalies of the oral cavity, jaws, and salivary glands. Despite the availability of numerous treatment modalities for oral disorders, a limited clinical response has been observed because of the inefficacy of the drugs and countless adverse side effects. Therefore, the development of safe, efficacious, and wide-spectrum therapeutics is imperative in the battle against oral diseases. Curcumin, extracted from the golden spice turmeric, is a well-known natural polyphenol that has been extensively studied for its broad pleiotropic attributes and its ability to modulate multiple biological processes. It is well-documented to target pro-inflammatory mediators like NF-κB, ROS, COX-2, IL-1, IL-2, TGF-β, growth factors, apoptotic proteins, receptors, and various kinases. These properties make curcumin a promising nutraceutical in the treatment of many oral diseases like oral submucous fibrosis, oral mucositis, oral leukoplakia, oral erythroplakia, oral candidiasis, aphthous stomatitis, oral lichen planus, dental caries, periodontitis, and gingivitis. Numerous in vitro and in vivo studies have shown that curcumin alleviates the symptoms of most of the oral complications, including the inhibition of the progression of oral cancer. In this regard, many clinical trials have been completed, and many are ongoing to investigate the “curcumin effect” in oral maladies. Therefore, the current review delineates the mechanistic framework of curcumin’s propensity in curbing oral diseases and present outcomes of the clinical trials of curcumin-based therapeutics that can provide a breakthrough in the clinical management of these diseases.

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“…85,109,110 PARP1/2 inhibitors are shown to be a better approach to target specific DDR in cancer, with good clinical response in many solid tumors, including HNSCC. [111][112][113] Nowadays, there are some PARP1/2 inhibitors approved by the FDA for clinical use, such as Olaparib, whose combination with other anticancer therapies for HNSCC is under investigation and shows promising results. 114 Despite the strong association of KMT2C/D members with the regulation of different pathways that could lead to tumor progression, disease aggressiveness, and DNA damage accumulation, besides its potential as a biomarker to predict immunotherapy response, further studies are needed to better clarify such mechanisms due to the heterogeneity found in this systematic review for both genes.…”

Section: Genetic Alterationsmentioning

confidence: 99%

KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review

da Silva Santos,

de Carvalho Abreu,

Martins da Silva

et al. 2023

Head & Neck

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BackgroundThe involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive.MethodThis study adhered to the PRISMA guidelines, employing a search strategy in the LIVIVO, PubMed, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological quality of the studies was assessed by the Joanna Briggs Institute.ResultsA total of 33 studies involving 4294 individuals with HNSCC were included in this review. The most important alteration was the high mutational frequency in the KMT2C and KMT2D genes, with reported co‐occurrence. The expression of the KMT2D gene exhibited considerable heterogeneity across the studies, while limited data was available for the remaining genes.ConclusionsKMT2C and KMT2D genes seem to have tumor suppressor activities, with involvement of cell cycle inhibitors, regulating different pathways that can lead to tumor progression, disease aggressiveness, and DNA damage accumulation.

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PARP inhibitor Olaparib Enhances the Apoptotic Potentiality of Curcumin by Increasing the DNA Damage in Oral Cancer Cells through Inhibition of BER Cascade

Cited by 21 publications

References 36 publications

Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor

Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor

From Simple Mouth Cavities to Complex Oral Mucosal Disorders—Curcuminoids as a Promising Therapeutic Approach

KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review

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