OSW-1 induces apoptosis and cyto-protective autophagy, and synergizes with chemotherapy on triple negative breast cancer metastasis

Wu, M. K.; Huang, Qianrui; Liao, Mengya; Wu, Xuyi; Xi, Huizhi; Ma, Huili; Li, Shanrui; Zhang, Yiwen; Xia, Yong

doi:10.1007/s13402-022-00716-2

Cited by 4 publications

(3 citation statements)

References 75 publications

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“…First, based on previous studies [ 12 , 20 ], we examined the expression of an ER stress-inducible proapoptotic factor, GADD153, in Neuro2a cells. We also analyzed the expression of LC3, since it was recently reported that OSW-1 induces autophagy in cancer cell lines [ 23 ]. As shown in Figure 1 C, 8 h of treatment with OSW-1 increased the amount of LC3-II, which is an autophagy marker, more profoundly, but the induction of GADD153, a well-known ER stress-inducible factor, was, to a lesser extent, compared with 8 h of treatment with BFA.…”

Section: Resultsmentioning

confidence: 99%

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells

Oh‐hashi

Nakamura

Ogawa

et al. 2023

IJMS

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OSW-1, a steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, is a promising compound for an anticancer drug; however, its cytotoxic mechanisms have not been fully elucidated. Therefore, we analyzed the stress responses triggered by OSW-1 in the mouse neuroblastoma cell line Neuro2a by comparing it with brefeldin A (BFA), a Golgi apparatus-disrupting reagent. Among the Golgi stress sensors TFE3/TFEB and CREB3, OSW-1 induced dephosphorylation of TFE3/TFEB but not cleavage of CREB3, and induction of the ER stress-inducible genes GADD153 and GADD34 was slight. On the other hand, the induction of LC3-II, an autophagy marker, was more pronounced than the BFA stimulation. To elucidate OSW-1-induced gene expression, we performed a comprehensive gene analysis using a microarray method and observed changes in numerous genes involved in lipid metabolism, such as cholesterol, and in the regulation of the ER–Golgi apparatus. Abnormalities in ER–Golgi transport were also evident in the examination of secretory activity using NanoLuc-tag genes. Finally, we established Neuro2a cells lacking oxysterol-binding protein (OSBP), which were severely reduced by OSW-1, but found OSBP deficiency had little effect on OSW-1-induced cell death and the LC3-II/LC3-I ratio in Neuro2a cells. Future work to elucidate the relationship between OSW-1-induced atypical Golgi stress responses and autophagy induction may lead to the development of new anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells

Oh‐hashi

Nakamura

Ogawa

et al. 2023

IJMS

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“…In addition, 6‐methoxydihydrosanguinarine (6‐MDS), a natural benzophenanthridine alkaloid, was reported to induce the apoptosis and autophagy of MCF‐7 cells by inducing reactive oxygen species (ROS) accumulation to inhibit the PI3K/AKT/mTOR pathway 40 . Moreover, OSW‐1[3β,16β,17α‐trihydroxycholest‐5‐en‐22‐one‐16‐O‐(2‐O‐4‐methoxybenzoyl‐β‐D‐xylopyranosyl)‐(1→3)‐(2‐O‐acetyl‐α‐L‐arabinopyranoside)] induces mitochondria‐dependent intrinsic apoptosis and cytoprotective autophagy through phosphatidylinositol‐3‐kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway in TNBC cells in vitro and in lung metastases in 4T1 mouse models in vivo 41 …”

Section: Discussionmentioning

confidence: 99%

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy

Chen

Chiu

Hung

et al. 2023

Environmental Toxicology

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Breast cancer is a leading cause of cancer‐related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose‐dependent manner and reduced colony formation, an index of clonogenicity. Annexin‐V and 7‐AAD double staining showed that DPDS could induce the apoptosis of breast cancer cells. Western blotting of the expression of Bax p21 and its cleaved form p18 suggested the activation of p18 Bax‐induced apoptosis. Furthermore, the increased expression of the autophagy marker LC3B‐II indicated autophagic lysosome accumulation induced by DPDS. Our findings suggest that DPDS has potential as a candidate for treating breast cancer, and further modifications and optimizations are warranted.

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“…Following treatment of TNBC cells with the specified reagents, alterations in protein expression profiles were assessed using Western blot analysis as previously outlined [ 32 ]. Subsequent to cell harvesting, cellular lysis was executed employing a cell lysate augmented with a protease inhibitor cocktail and maintained under refrigeration.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux

Huang,

Wu,

et al. 2024

Cancers

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The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.

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OSW-1 induces apoptosis and cyto-protective autophagy, and synergizes with chemotherapy on triple negative breast cancer metastasis

Cited by 4 publications

References 75 publications

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux

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