Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway

Gara, Rishi K.; Srivastava, Vikas; Duggal, Shivali; Bagga, Jaspreet Kaur; Bhatt, M L B; Sanyal, Sabyasachi; Mishra, Durga Prasad

doi:10.1186/s12929-015-0127-1

Cited by 62 publications

(55 citation statements)

References 45 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LPS-induced epithelial mesenchymal transition (EMT) was reduced by shikonin via inactivation of NF-κB signaling pathway [17]. Shikonin also induced the apoptosis of cancer cells through the dual induction of the endoplasmic reticulum (ER) stress and the mitochondrial dysfunction [18, 19]. The up-regulation of p73 and down-regulation of ICBP90 during the shikonin treatment also led to the apoptosis of human cancer cells [20].…”

Section: Introductionmentioning

confidence: 99%

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

Zhou

Yang

Wang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cholangiocarcinoma (CCA), arising from varying locations within the biliary tree, is the second most common primary liver malignancy worldwide. Shikonin, an active compound extracted from the Chinese herb Zicao, holds anti-bacterial, anti-inflammatory, and anti-tumor activities. However, the effect of shikonin on human cholangiocarcinoma and detailed mechanisms of TRAIL enhancement remains to be elucidated. The purpose of the study was to investigate the protective functions of TRAIL enhancement for shikonin induced apoptosis in cholangiocarcinoma cells. Methods: We use MTT assay, apoptosis assay, caspase activity assay, flow cytometry assay, real time PCR and Western blot to observe the effects of TRAIL on shikonin induced cholangiocarcinoma cells apoptosis and its mechanism. Results: Shikonin inhibited cell viability and induced apoptosis of CCA cells, effects enhanced by TRAIL treatment via activation of caspase-3, -8, -9. Furhermore, TRAIL enhanced anti-proliferation of shikonin and shikonin induced apoptosis through induction of ROS mediated JNK activation, while AKT activation had an effect on shikonin anti-proliferation activity, but not in the TRAIL enhanced counterparts. Finally, shikonin upregulated DR5 expression, an effect essential for TRAIL-enhanced activities of shikonin in RBE cells. Conclusions: Our results revealed that shikonin could inhibit cells viability and induce apoptosis of CCA cells, effects enhanced by TRAIL treatment via ROS mediated JNK signalling pathways, involving up-regulation of DR5 expression. Our results provide further insight into the mechanism underlying the anti-tumor effects of shikonin by TRAIL enhanced in CCA and a new therapeutic strategy to CCA treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

Zhou

Yang

Wang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Besides, SHI could selectively kill cancer cells by activating ER stress [25]. Therefore, we suspected that activation of ER stress contributes to HCC cell apoptosis by combined treatment.…”

Section: Resultsmentioning

confidence: 99%

Shikonin potentiates the effect of arsenic trioxide against human hepatocellular carcinomain vitroandin vivo

et al. 2016

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a highly lethal malignancy mostly because of metastasis, recurrence and acquired resistance to conventional chemotherapy. Arsenic trioxide (ATO) is successfully used to treat hematological malignancies, and has been proven to trigger apoptosis in HCC cells. However, the phase II trial evaluating the efficacy and toxicity of ATO in patients with HCC showed that single-agent ATO is poorly active against HCC. Therefore, it is of great importance to develop effective chemosensitization agents to ATO. The aim of the present study was to determine whether shikonin (SHI), a natural product from the root of lithospermum erythrorhizon, could synergistically enhance the anti-HCC efficacy of ATO both in vitro and in vivo. We found that the combination of SHI and ATO exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cells and normal cells. By inducing intracellular oxidative stress, SHI potentiated ATO-induced DNA damage, followed by increased activation of endoplasmic reticulum stress. In addition, inhibition of ROS reversed the apoptosis induced by SHI and ATO, and recovered the activation of endoplasmic reticulum stress, which revealed the vital role of ROS in the synergism. Moreover, HepG2 xenograft tumor growth in nude mice was more effectively inhibited by combined treatment with SHI and ATO. These data suggest that the combination of SHI with ATO presents a promising therapeutic approach for the treatment of HCC.

show abstract

“…STX is multifunctional protein inducing protein biosynthesis inhibition and endoplasmic reticulum (ER) stress response [18]. ER stress is widely reported to induce apoptotic cell death [19]. Thus, STX may enhance TNF-α induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α modifies the effects of Shiga toxin on glial cells

Leu

Sugimoto

Shimizu

et al. 2016

International Immunopharmacology

View full text Add to dashboard Cite

Shiga toxin (STX) is one of the main factors inducing hemorrhagic colitis and hemolytic-uremic syndrome (HUS) in infections with STX-producing Escherichia coli (STEC). Approximately 62% of patients with HUS showed symptoms of encephalopathy in the 2011 Japanese outbreak of STEC infections. At that time, we reported elevated serum concentrations of tumor necrosis factor (TNF)-α in patients with acute encephalopathy during the HUS phase. In the current study, we investigated whether TNF-α augments the effects of STX in glial cell lines and primary glial cells. We found that TNF-α alone or STX in combination with TNF-α activates nuclear factor-κB (NF-κB) signaling and inhibits growth of glial cells. The magnitude of the NF-κB activation and the inhibition of cell growth by the STX and TNF-α combination was greater than that obtained with TNF-α alone or STX alone. Thus, this in vitro study reveals the role of TNF-α in glial cells during STEC infections.

show abstract

Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway

Cited by 62 publications

References 45 publications

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

Shikonin potentiates the effect of arsenic trioxide against human hepatocellular carcinomain vitroandin vivo

Tumor necrosis factor-α modifies the effects of Shiga toxin on glial cells

Contact Info

Product

Resources

About