Unexpected therapeutic effects of cisplatin

Raudenská, Martina; Balvan, Jan; Fojtů, Michaela; Gumulec, Jaromír; Masařík, Michal

doi:10.1039/c9mt00049f

Cited by 82 publications

(68 citation statements)

References 214 publications

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“…From its first introduction in bedside oncology, different mechanisms of action for CDDP have been described [ 242 , 243 ]. Until most recently, an almost completely disregarded issue has been the fact that cisplatin significantly changes the pHi of cancer cells, inducing cytoplasmatic acidification through the inhibition of H + extrusion through NHE1 downregulation [ 241 , 242 , 244 , 245 ]. Indeed, this pHi-lowering effect has been considered to be the first effect of cisplatin on cancer cells [ 244 ].…”

Section: Other Ph-related Available Therapies In Breast Cancer Trementioning

confidence: 99%

“…Until most recently, an almost completely disregarded issue has been the fact that cisplatin significantly changes the pHi of cancer cells, inducing cytoplasmatic acidification through the inhibition of H + extrusion through NHE1 downregulation [ 241 , 242 , 244 , 245 ]. Indeed, this pHi-lowering effect has been considered to be the first effect of cisplatin on cancer cells [ 244 ]. Contrarily, the activity of NHE1 increases the resistance to cisplatin by elevating pHi [ 241 , 242 , 244 , 245 ], with this representing one more dualism of the pH paradigm.…”

Section: Other Ph-related Available Therapies In Breast Cancer Trementioning

confidence: 99%

See 1 more Smart Citation

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Harguindey¹,

Alfarouk

Orozco³

et al. 2020

IJMS

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A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this unitarian perspective, based upon the hydrogen ion (H+) dynamics of cancer, allows for the understanding and integration of the many dualisms, confusions, and paradoxes of the disease. The new H+-related, wide-ranging model can embrace, from a unique perspective, the many aspects of the disease and, at the same time, therapeutically interfere with most, if not all, of the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC reviewed here may be beneficial for all types and stages of the disease. In this vein, we have attempted a megasynthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide-ranging approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of the pH-related drugs that are available nowadays for the treatment of breast cancer is advanced.

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Section: Other Ph-related Available Therapies In Breast Cancer Trementioning

confidence: 99%

Section: Other Ph-related Available Therapies In Breast Cancer Trementioning

confidence: 99%

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Harguindey¹,

Alfarouk

Orozco³

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…From its first introduction in bedside oncology different mechanisms of action for CDDP have been described [267,268]. An almost completely disregarded issue in bedside oncology hs been the fact that CDDP can significantly modify the intracellular pH of cancer cells inducing cytoplasmatic acidification through a CDDP-mediated inhibition of H+ extrusion secondary to downregulation of NHE-1 [207,208,210,267] (Table 2).…”

Section: ) Hydrogen Ion Dynamics In Multiple Drug Resistance (Mdr) Imentioning

confidence: 99%

“…Contrariwise, the activity of NHE-1 and its effect on elevating pHi increases CDDP resistance to treatment [207]. Apart from inducing pHi acidification, CDDP shifts cervical cancer cells from glycolysis to oxidative metabolism, what is accompanied by inhibition of cancer cell growth.…”

Section: ) Hydrogen Ion Dynamics In Multiple Drug Resistance (Mdr) Imentioning

confidence: 99%

A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer based upon its Hydrogen Ion Dynamics

Harguindey¹,

Alfarouk

Orozco³

et al. 2019

Preprint

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Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

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“…The serendipitous discovery of the anticancer properties of cisplatin led to a paradigm shift in the clinical treatment of cancer. Although cisplatin and second generation platinum-based drugs are efficacious against many types of cancer [1][2][3][4], their use is associated with some restrictions, such as a limited selectivity leading to adverse side-effects and intrinsic or acquired resistance [5][6][7][8][9]. These limitations have fueled the research for the development of anticancer agents based on transition metals other than platinum [10][11][12][13][14][15][16][17][18][19][20][21], and in this respect mono-iron cyclopentadienyl compounds have been investigated, with substituted ferrocenes emerging as highly promising candidates [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity

Agonigi

Batchelor

Ferretti³

et al. 2020

Molecules

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A series of diiron/tetrairon compounds containing a S- or a Se-function (2a–d, 4a–d, 5a–b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)C2HC3(Me)}] (3) were prepared from the diiron μ-vinyliminium precursors [Fe2Cp2(CO)( μ-CO){μ-η1: η3-C3(R’)C2HC1N(Me)(R)}]CF3SO3 (R = R’ = Me, 1a; R = 2,6-C6H3Me2 = Xyl, R’ = Ph, 1b; R = Xyl, R’ = CH2OH, 1c), via treatment with S8 or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a–d, 5a–b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.

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Unexpected therapeutic effects of cisplatin

Abstract: Mechanisms of cisplatin antineoplastic action are beyond DNA binding. Alternative effects of cisplatin that can support a good therapeutic response are discussed in this review.

Cited by 82 publications

References 214 publications

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer based upon its Hydrogen Ion Dynamics

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity

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