Synergistic Effect of Vitamin C with Cisplatin for Inhibiting Proliferation of Gastric Cancer Cells

Ghavami, Ghazaleh; Sardari, Soroush

doi:10.29252/ibj.24.2.119

Cited by 19 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, it has been shown that vitamin C at pharmacologic plasma concentrations acquired intravenously can selectively kill the tumor cells but had little cytotoxic effect on normal cells; and these effect was mainly through a reactive oxygen species (ROS) dependent way [ 16 – 18 ]. These findings have inspired other studies to provide new insights into the function of combining therapy with vitamin C in treating different types of cancers [ 19 – 21 ]. Nevertheless, the function and the mechanism of combining therapy with vitamin C and PLX4032 in thyroid cancer has not been investigated yet.…”

Section: Introductionmentioning

confidence: 94%

Vitamin C sensitizes BRAFV600E thyroid cancer to PLX4032 via inhibiting the feedback activation of MAPK/ERK signal by PLX4032

Han

Hao

et al. 2021

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background BRAFV600E mutation is the most common mutation in thyroid cancer. It strongly activates MAPK/ERK pathway and indicates an invasive subtype of thyroid cancer. PLX4032 is a selective oral inhibitor of the BRAFV600 kinase although with limited effect in treating this panel of thyroid cancer, due to the feedback activation of MAPK/ERK as well as PI3K/AKT pathways. It was investigated that Vitamin C plays a positive role in inhibiting these pathways in thyroid cancer. However, whether Vitamin C could enhance the antitumor effect of PLX4032 remains largely unclear. Methods The antitumor efficacy of combination therapy with PLX4032 and Vitamin C on BRAFMT thyroid cancer cell was assessed by the MTT assay, EdU assay and colony formation, Chou-Talalay way was employed to analyze the synergistic effect. Flow cytometry were employed to assess cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Western blot and IHC were applied to investigate the mechanism underlying synergistic effect. Results PLX4032 or Vitamin C monotherapy was mildly effective in treating BRAFMT thyroid cancer cell and xenografts model. The combination therapy significantly inhibited cancer cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest compared to either monotherapy. PLX4032 monotherapy induced feedback activation of MAPK/ERK as well as PI3K/AKT pathway; while combination therapy significantly relieved this feedback. Conclusion Vitamin C promotes the antitumor effect of PLX4032 in BRAFMT thyroid cancer cell and xenografts model via relieving the feedback activation of MAPK/ERK as well as PI3K/AKT pathway. PLX4032/Vitamin C combination may be a potential therapeutic approach to treat BRAFMT thyroid cancer.

show abstract

Section: Introductionmentioning

confidence: 94%

Vitamin C sensitizes BRAFV600E thyroid cancer to PLX4032 via inhibiting the feedback activation of MAPK/ERK signal by PLX4032

Han

Hao

et al. 2021

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Ascorbic acid has been used in combination with cisplatin as an adjunctive treatment for many cancers [95][96][97][98]. It has a wide range of pharmacological effects including anticancer, anti-inflammatory, antioxidant, anti-diabetic, wound healing, and anti-osteoporotic effects.…”

Section: Ascorbic Acid (Vitamin C) and Cancer Treatmentmentioning

confidence: 99%

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy

Dasari

Njiki

Mbemi

et al. 2022

IJMS

142

View full text Add to dashboard Cite

Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.

show abstract

“…In pre-clinical models, high-dose VitC is reported to enhance the effectivity of a wide variety of chemotherapeutics such as carboplatin [ 63 , 89 ], cisplatin [ 51 , 89 , 100 – 103 , 179 , 180 ], chlorambucil [ 181 ], 5-FU [ 88 , 89 , 182 ], gemcitabine [ 14 , 110 , 183 , 184 ] and temozolomide [ 16 , 54 ] in various cancer cell types, often in a synergistic manner or by enhancing treatment efficacy (Table 1 and Fig. 2 ).…”

Section: High-dose Vitc In Combination Treatmentsmentioning

confidence: 99%

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer

Böttger

Vallés-Martí

Cahn

et al. 2021

J Exp Clin Cancer Res

110

View full text Add to dashboard Cite

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side-effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non-toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre-clinical and clinical studies using high-dose IVC as anti-cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high-dose vitamin C in cancer treatment is presented and recommendations for further research are discussed.

show abstract

Synergistic Effect of Vitamin C with Cisplatin for Inhibiting Proliferation of Gastric Cancer Cells

Cited by 19 publications

References 15 publications

Vitamin C sensitizes BRAFV600E thyroid cancer to PLX4032 via inhibiting the feedback activation of MAPK/ERK signal by PLX4032

Vitamin C sensitizes BRAFV600E thyroid cancer to PLX4032 via inhibiting the feedback activation of MAPK/ERK signal by PLX4032

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer

Contact Info

Product

Resources

About