Endoplasmic reticulum stress-induced apoptotic pathway and mitochondrial dysregulation in HeLa cells treated with dichloromethane extract of Dillenia suffruticosa

Abstract

Ethyl acetate and dichloromethane extract of Dillenia suffruticosa (EADS and DCMDS, respectively) can be a potential anticancer agent. The effects of EADS and DCMDS on the growth of HeLa cervical cancer cells and the expression of apoptotic-related proteins had been investigated in vitro. Cytotoxicity of the extracts toward the cells was determined by 5-diphenyltetrazolium bromide assay, the effects on cell cycle progression and the mode of cell death were analyzed by flow cytometry technique, while the effects on apoptotic-related genes and proteins were evaluated by quantitative real-time polymerase chain reaction, and Western blot and enzyme-linked immunosorbent assay, respectively. Treatment with DCMDS inhibited (P < 0.05) proliferation and induced apoptosis in HeLa cells. The expression of cyclin B1 was downregulated that led to G2/M arrest in the cells after treatment with DCMDA. In summary, DCMDS induced apoptosis in HeLa cells via endoplasmic reticulum stress-induced apoptotic pathway and dysregulation of mitochondria. The data suggest the potential application of DCMDS in the treatment of cervical cancer.

Induction of apoptosis and cell cycle arrest by flavokawain C on HT-29 human colon adenocarcinoma via enhancement of reactive oxygen species generation, upregulation of p21, p27, and Gadd153, and inactivation of inhibitor of apoptosis proteins

“…Overexpression of GADD153 has been shown to downregulate the antiapoptotic protein Bcl-2 and proapoptotic proteins (such as DR5, GADD34, Trb3, Bim, PUMA). [ 20 21 22 ] The present study showed that FKC induced an early expression of GADD153, and this is similar to our previous finding on HCT 116 cells. Thus, this could suggest the possibility that FKC initiate the apoptotic signaling via ER stress.…”

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

“…ER stress has also been linked with mitochondria-mediated apoptosis involving the Bcl-2 family of proteins. During ER stress, calcium released from the ER is taken up by the mitochondria, causing mitochondrial inner membrane depolarization and caspase-8 activation followed by the release of cytochrome c , which activates procaspase-9, which in turn activates caspase-3, DNA fragmentation, and cell death 33 . The increase of CHOP and spliced XBP1 mRNA expression and activation of Bcl2 family of proteins followed by DOE treatment indicates that DOE could induce ER stress in cancer cells.…”

Integrative Metabolomics, Genomics, and Transcriptomics Analysis Unravels Anti-Cancer Potential of Secondary Metabolites in Dillenia Suffruticosa

“…In addition, the leaves also reportedly possess antimicrobial, dengue antivirus, anti-in ammatory and anti-oxidant properties 3,6,11-13,36,37 . Among these pharmacological characteristics, the anti-cancer effects of D. suffruticosa are perhaps the most intriguing and have been reported to be e cacious in breast cancer and ovarian cancer cell-line studies 3,5,[13][14][15][16][17] . In addition to the cancer cell lines, we found that D. suffruticosa extracts are also selectively effective for cholangiocarcinoma, hepatocellular carcinoma, clear cell renal cell carcinoma, gastric cancer, colon cancer and lung cancer, with little toxic effects to normal kidney (HK2) cells and PBMCs.…”

“…suffruticosa has been leveraged for various pharmacological and ethnobotanical applications in traditional practices 2,6,[11][12][13] . Existing studies have illuminated the cytotoxic effects of D. suffruticosa extracts on breast and ovarian cancer cell lines 5,[13][14][15][16][17] . To bridge these knowledge gaps, this study aims to assemble the genome of D. suffruticosa, identify and understand the biosynthesis of its phytochemicals based on genomic and metabolic pro ling, and test the anti-cancer e cacy of extracts from different organs of D. suffruticosa against multiple cancer cell lines.…”