The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells

Naserian, Maryam; Ramazani, Elham; Iranshahi, Mehrdad; Tayarani‐Najaran, Zahra

doi:10.2174/1874467211666180830150546

Cited by 8 publications

(5 citation statements)

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“…Previous studies have revealed that TNF-α and IL-6 are involved in the mitogen-activated protein kinase (MAPK) pathway. Thus, co-treatment with ORT and DTIC may modulate the MAPK pathway ( 36 ). The levels of IL-6 and TNF-α were downregulated in RAW264.7 cells, suggesting that the combination of ORT and DTIC could exert synergistic effects in vitro and in vivo , which might allow the coexistence of cancer and immune cells.…”

Section: Discussionmentioning

confidence: 99%

Synergistic inhibitory effects of the oxyresveratrol and dacarbazine combination against melanoma cells

et al. 2021

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Various therapies have been developed to target malignant melanoma, which is associated with a high mortality rate worldwide. Although dacarbazine (DTIC) is employed for treating melanoma, it is associated with several side effects. Hence, patients with melanoma are co-treated with additional drugs to mitigate the side effects of DTIC. In the present study, synergistic therapeutic effects of the DTIC/oxyresveratrol (ORT) combination were examined using the human malignant melanoma WM-266-4 cell line. Treatment with ORT and DTIC inhibited the proliferation of WM-266-4 cells. Compared with those in the ORT-and DTIC-treated groups, the proportion of cells arrested at the S phase, as well as apoptotic rates, were increased in the ORT and DTIC co-treatment group. In WM-266-4 cells, synergistic proliferation-inhibitory activities of the ORT/DTIC combination were assessed based on cell viability and migration, antioxidant capacity, cytokine production, cell cycle arrest, apoptotic rate and protein expression through WST-1 assay, wound healing assay, flow cytometry and western blotting. Furthermore, the expression levels of proteins, including NOTCH, involved in the pathogenesis of solid cancers, such as melanoma, were examined. Overall, the ORT/DTIC combination synergistically promoted cell cycle arrest at the S phase and the apoptosis of WM-266-4 cells. Thus, this combination treatment may serve as a novel therapeutic strategy for treating malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Synergistic inhibitory effects of the oxyresveratrol and dacarbazine combination against melanoma cells

et al. 2021

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“…Naserian et al. reported that combination of metformin with dacarbazine notably induced the apoptosis in Raji cells via activation of JNK signaling ( 58 ). Prolonged JNK activation contributes to cell apoptosis ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, our data found that combination treatment caused no difference in the activation of p38 and ERK1/2 in Raji cells, while combination treatment significantly increased the phosphorylation level of JNK in Raji cells. He (58). Prolonged JNK activation contributes to cell apoptosis (59).…”

Section: Discussionmentioning

confidence: 99%

Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway

Xiang

Zhu

et al. 2021

Front. Oncol.

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BackgroundBoth omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells.MethodsCell counting kit-8 (CCK-8), Ki67 immunofluorescence and transwell assays were used to assess the viability, proliferation and migration of U937 and Raji cells respectively. In addition, tube formation assay was used to determine the effects of HHT/curcumin combination on angiogenesis in human umbilical vein endothelial cells (HUVECs).ResultsIn this study, we found that HHT/curcumin combination significantly inhibited the proliferation, migration and invasion in U937 and Raji cells (all P < 0.01). In addition, combination treatment markedly inhibited the secreted levels of vascular endothelial growth factor (VEGF)-(A-D) (all P < 0.01) in Raji cells. Moreover, combination treatment exhibited anti-tumor effects in Raji cells, as shown by the decreased signals of phosphorylated VEGF receptor 2 (p-VEGFR2) and phosphorylated protein kinase B (p-Akt) (all P < 0.01). Meanwhile, combination treatment inhibited VEGFA levels (P < 0.01) in exosomes derived from Raji cells. Application of exosomes with downregulated VEGF to HUVECs notably inhibited proliferation, migration and tube formation of HUVECs, evidenced by the decreased signals of p-Akt, angiogenin-1, matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) (all P < 0.01).ConclusionOur findings indicated that combination of HHT and curcumin could inhibit lymphoma cell growth and angiogenesis via inhibition of VEGF/Akt signaling pathway. These results suggested that HHT combined with curcumin might be regarded as a promising therapeutic approach for the treatment of lymphoma.

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“…Shi et al provided evidence of the ex vivo activity of metformin acting on human lymphoma cells, demonstrating that the metformin activation of AMPK inhibits the growth of B-and T-cell lymphomas via the inhibition of mTOR signaling, suggesting that metformin can be used in the treatment of lymphoma [193]. At the same time, metformin can enhance the tumor suppressive effect of common drugs for treatments such as asdriamycin, dacarbazine, venetoclax and rituximab [200,230,287].…”

Section: Lymphomamentioning

confidence: 99%

Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review

et al. 2023

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Hematologic malignancies (HMs) mainly include acute and chronic leukemia, lymphoma, myeloma and other heterogeneous tumors that seriously threaten human life and health. The common effective treatments are radiotherapy, chemotherapy and hematopoietic stem cell transplantation (HSCT), which have limited options and are prone to tumor recurrence and (or) drug resistance. Metformin is the first-line drug for the treatment of type 2 diabetes (T2DM). Recently, studies identified the potential anti-cancer ability of metformin in both T2DM patients and patients that are non-diabetic. The latest epidemiological and preclinical studies suggested a potential benefit of metformin in the prevention and treatment of patients with HM. The mechanism may involve the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway by metformin as well as other AMPK-independent pathways to exert anti-cancer properties. In addition, combining current conventional anti-cancer drugs with metformin may improve the efficacy and reduce adverse drug reactions. Therefore, metformin can also be used as an adjuvant therapeutic agent for HM. This paper highlights the anti-hyperglycemic effects and potential anti-cancer effects of metformin, and also compiles the in vitro and clinical trials of metformin as an anti-cancer and chemosensitizing agent for the treatment of HM. The need for future research on the use of metformin in the treatment of HM is indicated.

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The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells

Cited by 8 publications

References 0 publications

Synergistic inhibitory effects of the oxyresveratrol and dacarbazine combination against melanoma cells

Synergistic inhibitory effects of the oxyresveratrol and dacarbazine combination against melanoma cells

Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway

Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review

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