Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

Wu, Songjiang; Yz, Yang; Huang, Lifu; Han, Zhengxue; Wang, Guanfu; Yu, Hongyuan; Li, Haiping

doi:10.2147/ott.s157707

Cited by 29 publications

(22 citation statements)

References 42 publications

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“…PCa is known as the most frequent non-cutaneous cancer and the second main cause of cancer-related mortality in all the countries [ 21 ]. The challenges for the treating the patients with PCa are because of the shortage of understanding the molecule mechanism of PCa.…”

Section: Discussionmentioning

confidence: 99%

MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway

Gao

Zhao

et al. 2018

Aging

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Prostate cancer (PCa) is considered as a common visceral cancer in males and the sixth major cause of cancer-related deaths in males worldwide. Significant diagnostic and therapeutic advances have been made in the past decades. However, an improved understanding of their molecular mechanism is still needed. In the present research, we first detected the expression of miR-146b by quantitative real-time PCR (qRT-PCR) and found that miR-146b expression was increased in PCa. Subsequently, we found that miR-146b play an important role in the viability and proliferation capacity of PCa cells functionally. To explore the mechanism, we performed western blot to examine the autophagy-related markers, and found that miR‑146b may promote autophagy in PCa cells via activation of PTEN/AKT/mTOR signaling pathway. Furthermore, we performed the dual luciferase reporter assay to clarify the relationship between miR-146b and PTEN. In conclusion, this study demonstrated that miR-146b inhibited autophagy in PCa by targeting the PTEN/Akt/mTOR signaling pathway, and it could be a potential candidate for application in the treatment of PCa.

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Section: Discussionmentioning

confidence: 99%

MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway

Gao

Zhao

et al. 2018

Aging

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“…Previous studies have proved that CHE causes prostate cancer cell apoptosis mainly related to the activation of ER stress signalling pathway. 16 Besides, it has been report that oxidative stress modulating drugs activate the ER stress-related apoptosis. 18 Thus, we speculated that ER stress contributed to renal cancer cells apoptosis by CHE treatment.…”

Section: Che Caused Ros-dependent Er Stress Activation In Human Renmentioning

confidence: 99%

Chelerythrine induces apoptosis via ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma

Zhuo

Dai

et al. 2019

J Cellular Molecular Medi

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Renal cell carcinoma (RCC) is a heterogeneous histological disease and it is one of the most common kidney cancer. The treatment of RCC has been improved for the past few years, but its mortality still remains high. Chelerythrine (CHE) is a natural benzo[c]phenanthridine alkaloid and a widely used broad‐range protein kinase C inhibitor which has anti‐cancer effect on various types of human cancer cells. However, its effect on RCC has not been fully elucidated. In this study, we evaluated the effect and mechanism of CHE on RCC cells. Our study showed that CHE induced colony formation inhibition and G2/M cell cycle arrest in a dose‐dependent manner in RCC cells. In addition, CHE increased cellular ROS level, leading to endoplasmic reticulum (ER) stress, inactivating STAT3 activities and inducing apoptosis in RCC cells which were suppressed by NAC, a special ROS inhibitor. We further found that both knockdown of ATF4 protein and overexpression of STAT3 protein could reduce CHE‐induced apoptosis in Caki cells. These results demonstrated that the apoptosis induced by CHE was mediated by ROS‐caused ER stress and STAT3 inactivation. Collectively, our studies provided support for CHE as a potential new therapeutic agent for the management of RCC.

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“…In the case of chelerythrine chloride treatment, there could be involvement of ROS generation beyond what the intrinsic cellular antioxidants could handle, thus leading to oxidative stress and cell death. Indeed, several studies including in NSCLC, prostate cancer and renal cell carcinoma confirmed that chelerythrine-induced cell death was mediated through ROS generation and was reversible upon pre-treatment of the ROS scavenging agent-N-acetyl-l-cysteine (NAC) [22,23,50]. Different type of cell death can ensue depending on the amount of ROS generated.…”

Section: Discussionmentioning

confidence: 99%

“…Studies over the years have successfully established the apoptotic-inducing ability of chelerythrine in a variety of cancer cells, namely in uveal melanoma, leukemia, prostate cancer, hepatoma, and renal cancer [17][18][19][20][21]. The latest reports suggest apoptosis is mediated through reactive oxygen species (ROS)-dependent endoplasmic reticulum (ER) stress induction and possibly through signal transducer and activator of transcription 3 (STAT3) inactivation [22,23]. Studies also showed that chelerythrine was able to inhibit the growth of cisplatin-resistant NSCLC and triple-negative breast cancer cells as well as sensitizing them to chemotherapies [24,25].…”

Section: Introductionmentioning

confidence: 99%

Chelerythrine Chloride Downregulates β-Catenin and Inhibits Stem Cell Properties of Non-Small Cell Lung Carcinoma

Heng

Cheah

2020

Molecules

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Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology—the lung malignancy that kills an estimated two million people annually. In the present study, we characterized a medicinal compound benzophenanthridine alkaloid, called chelerythrine chloride for its anti-tumorigenic activities. Cell viability assays confirmed its cytotoxicity and anti-proliferative activity in non-small cell lung carcinoma (NSCLC) cell lines. Immunofluorescence staining of β-catenin revealed that there was a reduction of nuclear content as well as overall cellular content of β-catenin after treating NCI-H1703 with chelerythrine chloride. In functional characterizations, we observed favorable inhibitory activities of chelerythrine chloride in cancer stem cell (CSC) properties, which include soft agar colony-forming, migration, invasion, and spheroid forming abilities. Interesting observations in chelerythrine chloride treatment noted that its action abides to certain concentration-specific-targeting behavior in modulating β-catenin expression and apoptotic cell death. The downregulation of β-catenin implicates the downregulation of CSC transcription factors like SOX2 and MYC. In conclusion, chelerythrine chloride has the potential to mitigate cancer growth due to inhibitory actions toward the tumorigenic activity of CSC in lung cancer and it can be flexibly adjusted according to concentration to modulate specific targeting in different cell lines.

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Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

Cited by 29 publications

References 42 publications

MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway

MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway

Chelerythrine induces apoptosis via ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma

Chelerythrine Chloride Downregulates β-Catenin and Inhibits Stem Cell Properties of Non-Small Cell Lung Carcinoma

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