Thymoquinone Potentiated the Anticancer Effect of Cisplatin on Hepatic Tumorigenesis by Modulating Tissue Oxidative Stress and Endoplasmic GRP78/CHOP Signaling

2021 ◽  
pp. 1-10
Author(s):  
Maha Eid Farghaly ◽  
Akef Abdelhalim Khowailed ◽  
Basma Emad Aboulhoda ◽  
Laila Ahmed Rashed ◽  
Safy Salah Gaber ◽  
...  
Author(s):  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Mohammad S. Mubarak ◽  
Divya Jain ◽  
Rasel Khan ◽  
...  

Background: Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. Objective: To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. Method: Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. Result: Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit ‎antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. Conclusions: Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.


2018 ◽  
Vol 17 (4) ◽  
pp. 1235-1246 ◽  
Author(s):  
Abdelnaser A. Badawy ◽  
Mohammed A. El-Magd ◽  
Sana A. AlSadrah

Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.


2019 ◽  
Vol 18 (12) ◽  
pp. 2373-2387 ◽  
Author(s):  
Xuepei Zhang ◽  
Massimiliano Gaetani ◽  
Alexey Chernobrovkin ◽  
Roman A. Zubarev

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Keqing He ◽  
Xing Liu ◽  
Shiping Cheng ◽  
Pingsheng Zhou

Objective. Saponins are a group of compounds from various plants, which exhibit an anticancer activity. This study aimed to explore the anticancer effect of zingiberensis newsaponin (ZnS) against hepatocellular carcinoma (HCC) and the underlying mechanism involving autophagy. Methods. HCC cells (Huh7 and SMMC7721) were treated with ZnS and/or 3-MA. The cell viability, migration, and apoptosis were determined using CCK-8 assay, transwell assay, and flow cytometry, respectively. The levels of oxidative stress markers (ROS, SOD, and MDA) were measured by ELISA assay. Autophagy was monitored using MDC assay, immunofluorescence staining, and transmission electron microscopy. The relative protein expression of LC3II/LC3I, P62, AKR1C1, p-JAK2, p-STAT3, JAK2, and STAT3 was determined using Western blot. Results. ZnS or 3-MA inhibited the cell viability and migration, and it promoted cell apoptosis and oxidative stress in HCC. MDC-positive cells and autophagosomes were reduced by ZnS or 3-MA treatment. The expression of autophagy-related proteins LC3 (LC3II/LC3I) and P62 was, respectively, downregulated and upregulated after ZnS or 3-MA treatment. In addition, ZnS or 3-MA suppressed the protein expression of AKR1C1, p-JAK2, and p-STAT3 in HCC cells. Furthermore, the above phenomena were evidently enhanced by ZnS combined 3-MA treatment. AKR1C1 overexpression weakened the effect of ZnS on inhibiting the expression of AKR1C1, p-JAK2, and p-STAT3. Conclusion. ZnS exerts an anticancer effect on HCC via inhibiting autophagy moderated by the AKR1C1-mediated JAK2/STAT3 pathway. ZnS and 3-MA exert a synergistic effect on inhibiting HCC.


Author(s):  
İsmail Koyuncu ◽  
Ataman Gönel ◽  
Ebru Temiz ◽  
Eyyüp Karaoğul ◽  
Zafer Uyar

Background: Pistachio is considered to be one of the fifty foods with the highest antioxidant effect. However, the anticancer effect mechanisms of this plant extracts are unknown. Objective: The aim of this study is to investigate the anticancer effect of different extracts from green hull of pistachio. Methods: The cytotoxic effects of different solvent extracts on cancer and normal cells were examined by cell viability assay and flow cytometric analysis. The levels of apoptoticgene and protein were investigated by Western Blot and ELISA,and qPCR. Intracellular free radical exchange was determined by oxidativeand nitric oxide analyses. DNA damage level was measured by 8-OHdG test. Phenolic and free fatty acid components were examined by LC-MS/MS and GC-MS, respectively. Results: It was determined that n-hexane fraction showed the highercytotoxic effect on cancer cells. Oxidative and cell cycle analyses indicated that the n-hexane fraction arrested cell cycle of HT-29 at the sub-G1 phase by increasing DNA damage through oxidative stress. In addition, gene expression analysis of the HT-29 treated with the n-hexane fraction indicated that apoptotic and autophagic gene expressions were significantly up-regulated. LC-MS/MS analysis of then-hexane fraction revealed the presence of 15 phenolic compounds, containing mainly gallic acid and catechin hydrate, and GC-MS analysis determined presence of the following fatty acids:9-octadecenoic acid, 9,12-octadecadienoic acid and hexadecenoic acid. Conclusion: Based on these grounds, we suggest that n-hexane fraction of pistachio green hull damages DNA, arrests the cell cycle at the G1 sub phase, and induces apoptosis through oxidative pathways in colon cancer.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Zhao ◽  
Yan Liu ◽  
Xi-Ming Lan ◽  
Guo-Liang Xu ◽  
You-Zhi Sun ◽  
...  

Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.


Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
E Kim ◽  
J Hong ◽  
J Kang ◽  
D Park ◽  
Y Koh ◽  
...  

2019 ◽  
Vol 38 (6) ◽  
pp. 703-712 ◽  
Author(s):  
AE El-Sisi ◽  
SS Sokar ◽  
ME El-Sayad ◽  
EA Moussa ◽  
EI Salim

Objectives: Metformin, the type 2 anti-diabetes medication, showed antitumor activity both in vivo and in vitro. This study was carried out to investigate the mechanisms behind the metformin anticancer effect against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female Sprague-Dawley rats. Methods: Rats received 10 doses of PhIP (75 mg/kg, p.o., days 1–5 and 8–12). Then, rats were treated with metformin for 26 weeks at a dose of 2 mg/ml in drinking water. Key findings: Metformin antitumor effect was mediated by increasing the adenosine monophosphate protein kinase (AMPK) activity, liver kinase B1, and decreasing the aromatase and insulin levels compared with the PhIP-administered group. Also, this treatment resulted in a significant decrease in mammary tissue oxidative stress markers and serum lipid profile. In parallel, mammary gland tumors found in PhIP+metformin group were all histologically benign included only (hyperplasia). However, most of the mammary gland tumors found in PhIP group were histologically malignant. Conclusions: These results showed that metformin antitumor effect was mediated through AMPK pathway, reducing oxidative stress and serum lipid levels. This study supports the potential benefit of using metformin as adjuvant therapy during breast cancer treatment.


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