Induction of apoptosis by Shikonin through ROS-mediated intrinsic and extrinsic apoptotic pathways in primary effusion lymphoma

Alam, Masud; Kariya, Ryusho; Boonnate, Piyanard; Kawaguchi, Azusa; Okada, Seiji

doi:10.1016/j.tranon.2020.101006

Cited by 9 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance, we demonstrated that shikonin induced G2/M phase arrest, down-regulated protein level of Bcl-2, along with increased protein level of cleaved-PARP and cleaved-caspase-3/9 suggesting that apoptosis was elevated in both HCT-116 and HCT-15 cells. Study has reported that Shikonininduced apoptosis through the mitochondrial pathway, and generation of reactive oxygen species, the activation of c-Jun-N-terminal kinase (JNK), p38, caspase-3/9 and the cleavage of PARP [29].…”

Section: Discussionmentioning

confidence: 99%

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Qi¹,

Zhang²,

Liu³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

Shikonin is a naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon, which has displayed potent anti-tumor properties. However, the effects of shikonin in colorectal cancer cells have not been yet fully investigated. In this study, we demonstrated that shikonin significantly inhibited the activity of colorectal cancer cells in a time-and dose-dependent manner. The flow cytometry and western blot results indicated that shikonin induced cell apoptosis by down-regulating BCL-2 and activating caspase-3/9 and the cleavage of PARP. The expression of BiP and the PERK/elF2α/ATF4/CHOP and IRE1α /JNK signaling pathways were upregulated after shikonin treatment. The pre-treatment with N-acetyl cysteine significantly reduced the cytotoxicity of shikonin. Taken together, shikonin could inhibit proliferation of the colorectal cancer cell through the activation of ROS mediated-ER stress. The in vivo results showed that shikonin effectively inhibited tumor growth in the HCT-116 and HCT-15 xenograft models. In conclusion, shikonin inhibited the proliferation of colorectal cancer cells in vitro and in vivo and warrants future investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Qi¹,

Zhang²,

Liu³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Accumulation of ROS causes depolarization of the mitochondrial membrane potential (ΔΨm). A previous report [ 17 ] showed that SHK accelerates ROS accumulation, disrupting the mitochondrial membrane and inducing apoptosis. We examined the ΔΨm in ED− cells and TL-Om1 cells after SHK treatment using JC-1 dye, a lipophilic cationic carbocyanine dye that accumulates in mitochondria.…”

Section: Resultsmentioning

confidence: 99%

“…SHK is a ROS inducer, and accumulation of ROS in cancer cells plays an important role upstream of the apoptosis pathway [ 39 ]. SHK induces ROS-related apoptotic cell death in human prostate cancer [ 26 ] and primary effusion lymphoma [ 17 ]. We showed that ROS accumulated in ATLL cells with SHK treatment and induced cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Shikonin (SHK) is the major chemical component of Lithospermum erythrorhizo , and has a broad range of pharmacological activities including anti-inflammatory, anti-oxidative stress, anti-virus, anti-bacteria, and anti-cancer effects [ 13 , 14 , 15 ]. The anti-cancer effect of SHK by induction of reactive oxygen species (ROS) has recently drawn attention [ 16 , 17 , 18 ], modulating cancer survival pathways such as PI3K/AKT/mTOR and MAPKs signaling [ 14 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Shikonin Induces ROS-Dependent Apoptosis Via Mitochondria Depolarization and ER Stress in Adult T Cell Leukemia/Lymphoma

2023

Self Cite

View full text Add to dashboard Cite

Adult T cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy that develops in some elderly human T-cell leukemia virus (HTVL-1) carriers. ATLL has a poor prognosis despite conventional and targeted therapies, and a new safe and efficient therapy is required. Here, we examined the anti-ATLL effect of Shikonin (SHK), a naphthoquinone derivative that has shown several anti-cancer activities. SHK induced apoptosis of ATLL cells accompanied by generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and induction of endoplasmic reticulum (ER) stress. Treatment with a ROS scavenger, N-acetylcysteine (NAC), blocked both loss of mitochondrial membrane potential and ER stress, and prevented apoptosis of ATLL cells, indicating that ROS is an upstream trigger of SHK-induced apoptosis of ATLL cells through disruption of the mitochondrial membrane potential and ER stress. In an ATLL xenografted mouse model, SHK treatment suppressed tumor growth without significant adverse effects. These results suggest that SHK could be a potent anti-reagent against ATLL.

show abstract

“…Chicken anaemia virus features three open reading frames that encode three proteins VP1 (capsid protein: 51.6 kDa), VP2 (scaffold protein: 24.0 kDa) and VP3 (apoptosis‐inducing protein: 13.6 kDa). The protein expressed by VP3 is referred to as ‘apoptin’ because it can induce apoptosis in tumour cells 21 , 22 but has no effect on normal diploid cells in humans. Telomerase is mainly responsible for the de novo synthesis of nucleotides that are used to extend the ends of chromosomes that are found in germ cells and most malignant cells.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of the ability of recombinant oncolytic adenovirus, doxorubicin and tamoxifen to inhibit the proliferation of breast cancer cells

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

In this study, we compared the inhibitory effects of recombinant oncolytic adenovirus (Ad‐apoptin‐hTERTp‐E1a, Ad‐VT) with that of doxorubicin (DOX), a first‐line chemotherapy drug, and tamoxifen (TAM), an endocrine therapy drug, on the proliferation of breast cancer cells. We found that Ad‐VT could effectively inhibit the proliferation of breast cancer cells ( p < 0.01); the inhibition rate of Ad‐VT on normal mammary epithelial MCF‐10A cells was less than 20%. DOX can effectively inhibit the proliferation of breast cancer cells and also has a strong inhibitory effect on MCF‐10A cells ( p < 0.01). TAM also has a strong inhibitory effect on breast cancer cells, among which the oestrogen‐dependent MCF‐7 cell inhibition was stronger ( p < 0.01), At higher concentrations, TAM also had a high rate of inhibition (>70%) on the proliferation of MCF‐10A cells. We also found that both recombinant adenovirus and both drugs could successfully induce tumour cell apoptosis. Further Western blot results showed that the recombinant adenovirus killed breast cancer cells through the endogenous apoptotic pathway. Analysis of the nude mouse subcutaneous breast cancer model showed that Ad‐VT significantly inhibited tumour growth (the luminescence rate of cancer cells was reduced by more than 90%) and improved the survival rate of tumour‐bearing mice ( p < 0.01). Compared with DOX and TAM, Ad‐VT has a significant inhibitory effect on breast cancer cells, but almost no inhibitory effect on normal breast epithelial cells, and this inhibitory effect is mainly through the endogenous apoptotic pathway. These results indicate that Ad‐VT has significant potential as a drug for the treatment of breast cancer.

show abstract

Induction of apoptosis by Shikonin through ROS-mediated intrinsic and extrinsic apoptotic pathways in primary effusion lymphoma

Cited by 9 publications

References 51 publications

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Shikonin Induces ROS-Dependent Apoptosis Via Mitochondria Depolarization and ER Stress in Adult T Cell Leukemia/Lymphoma

A comparative study of the ability of recombinant oncolytic adenovirus, doxorubicin and tamoxifen to inhibit the proliferation of breast cancer cells

Contact Info

Product

Resources

About