Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

Paucarmayta, Ana; Taitz, Hannah; McGlorthan, Latoya; Casablanca, Yovanni; Maxwell, G. Larry; Darcy, Kathleen M.; Syed, Viqar

doi:10.3390/biomedicines8040073

Cited by 7 publications

(6 citation statements)

References 58 publications

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“…Obviously, PI3K/AKT and MAPK/ERK pathways are important components that regulate cancer cell proliferation, migration, and metastasis. In addition, many studies have shown that DDP resistance is related to altered cancer cell signaling pathways, including PI3K/AKT and MAPK/ERK pathways (24,25). Therefore, we investigated whether the effect of CB in promoting DDP sensitivity is related to PI3K/AKT and MAPK/ERK signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Cinobufagin Enhances the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibiting the PI3K/AKT and MAPK/ERK Pathways

Zhang

Liu

Wang³

et al. 2021

Preprint

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Background: Lung cancer patients always develop serious chemotherapy resistance after long-term use of cisplatin (DDP) treatment. It has been demonstrated that combination of DDP with other chemotherapy drugs may significantly reduce drug resistance. Cinobufagin (CB) showed potent anti-tumor effect against lung cancer. However, the relevance of CB and DDP resistance in lung cancer remains unclear. This article will study the effects of CB on reversing lung cell resistance in vitro and in vivo. Materials and Methods: The cell viability was evaluated using the Cell Counting Kit 8 (CCK8) assay. The apoptosis was detected by flow cytometry analysis and TUNEL staining. The invasiveness was detected by Invasion assay. The mRNA and protein of apoptosis-related proteins, P-AKT, P-PI3K, P-MEK1/2, P-ERK1/2 and MRP1 were estimated by qRT-PCR analysis and western blot analysis, respectively. In vivo antitumor activities were investigated by subcutaneous xenograft assay. Results: The present study firstly demonstrated that the sensitivity of DDP in DDP-resistant A549 (A549/DDP) cells was enhanced when treatment with CB. Moreover, CB combined with DDP significantly weakened the proliferation and increased apoptosis of A549/DDP cells. In addition, the expression level of Bcl-2 was increased, whereas Bax and Caspase-3 were activated when A549/DDP cells were treated with both drugs. Moreover, after treatment with IGF1 (activator of PI3K/AKT) or PMA (activator of MAPK/ERK) and mixed drugs (CB+DDP), the expressions of P-AKT, P-PI3K, P-MEK1/2 and P-ERK1/2 were increased. Finally, the results of in vivo experiments showed that the combination of DDP and CB significantly reduced the growth of tumors derived from A549/DDP cells. Conclusions: In summary, the results of this study indicate that the combination of CB and DDP can be considered an effective strategy to increase the sensitivity of DDP-resistant lung cancer cells to DDP by inhibiting the PI3K/AKT and MAPK/ERK pathways.

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Section: Discussionmentioning

confidence: 99%

Cinobufagin Enhances the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibiting the PI3K/AKT and MAPK/ERK Pathways

Zhang

Liu

Wang³

et al. 2021

Preprint

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“…Meanwhile, calcitriol significantly inhibited the expression of NLRP3 inflammasome-related genes and IL-1β production in hyperosmotic stress (HS)-exposed cells ( Dai et al, 2019 ). In addition, the combination of progesterone and calcitriol significantly inhibited the growth of endometrial and ovarian cancer cells ( Paucarmayta et al, 2020 ). The results of our study showed that calcitriol levels in the B. fragilis group were significantly higher than those in the control group, and vaginal administration also significantly altered steroid and steroid hormone biosynthesis according to KEGG.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Analysis After Vaginal Administration of Bacteroides fragilis in Chickens

Yang

Zhu

et al. 2022

Front. Microbiol.

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The reproductive tract of chickens is an important organ for egg formation. The vagina is in close contact with the external environment, which may lead to the invasion of a variety of pathogenic bacteria, affect the internal and external quality of eggs, and even increase mortality and cause economic loss. In recent years, probiotics as a substitute for antibiotics have brought economic benefits in livestock and poultry production. In the present study, we investigated the effects of vaginal administration of Bacteroides fragilis on the cloacal microbiota, vaginal transcriptome and metabolomics of chickens and evaluated the beneficial potential of B. fragilis. The results showed that B. fragilis treatment could affect the microbial composition of the cloaca. Transcriptome analysis found that the immune-related genes CCN3, HAS2, and RICTOR were upregulated, that the inflammatory genes EDNRB, TOX, and NKX2-3 were downregulated, and that DEGs were also enriched in the regulation of the inflammatory response, cellular metabolism, and synaptic response pathways. In addition, the differential metabolites were mainly related to steroid hormone biosynthesis, unsaturated fatty acid biosynthesis, and arachidonic acid metabolism, and we identified associations between specific differential metabolites and genes. Overall, this study provides a theoretical basis for the application of B. fragilis as a potential probiotic in livestock and poultry production.

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Section: Ovarian Cancermentioning

confidence: 99%

“…An in vitro study on ovarian cancer cells revealed that a combination of progesterone, calcitriol, and cisplatin significantly enhanced the effectiveness of anticancer therapy [55]. The triple-drug combination was observed to promote apoptosis by downregulating the expression of BCL2 and PARP-1, upregulating caspase-3 and BAX, and inhibiting the PI3K/AKT and MAPK/ERK signaling pathways [55]. Additionally, a reduction in the expression of SMAD2/3, ABC transporters (ABCG1 and ABCG2), and the multidrug resistance protein-1 (MDR-1) was associated with increased responsiveness to treatment [55].…”

Section: Ovarian Cancermentioning

confidence: 99%

“…The triple-drug combination was observed to promote apoptosis by downregulating the expression of BCL2 and PARP-1, upregulating caspase-3 and BAX, and inhibiting the PI3K/AKT and MAPK/ERK signaling pathways [55]. Additionally, a reduction in the expression of SMAD2/3, ABC transporters (ABCG1 and ABCG2), and the multidrug resistance protein-1 (MDR-1) was associated with increased responsiveness to treatment [55]. Paucarmayta et al have suggested using TGF-β and CYP24A1 signaling proteins to monitor the effectiveness of combination therapy with progesterone and calcitriol [55].…”

Section: Ovarian Cancermentioning

confidence: 99%

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Vitamins in Gynecologic Malignancies

Wierzbowska,

Olszowski,

Chlubek

et al. 2024

Nutrients

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The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.

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Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

Cited by 7 publications

References 58 publications

Cinobufagin Enhances the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibiting the PI3K/AKT and MAPK/ERK Pathways

Cinobufagin Enhances the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibiting the PI3K/AKT and MAPK/ERK Pathways

Multi-Omics Analysis After Vaginal Administration of Bacteroides fragilis in Chickens

Vitamins in Gynecologic Malignancies

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