Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2

Hu, Chunjie; Zhou, Lei; Cai, Yan

doi:10.4161/cbt.27223

Cited by 62 publications

(50 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies revealed that DHA and Cur treatment alone delayed the growth of ovarian cancer, including a dose-dependent G2/M arrest [33, 34]. In addition, targeting the Bcl-2 family-mediated apoptosis components was an important mechanism for the antitumor activity of DHA in cancer cells, and Cur could potentiate the anticancer effect of chemotherapy for cell apoptosis [35, 36]. Consistent with previous reports, our results also indicated that elevated apoptosis in the co-treatment of DHA and Cur group was accompanied by a decrease of Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine

Zhao

Pan

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aim: Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). Methods: Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis. Results: Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3ʹ-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity. Conclusion: Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine

Zhao

Pan

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…ME-180 cells were seeded at a density of 4 Â 10 4 cells per 100 ml per well of a 96-well plate and incubated for 24 h. Cells were subsequently treated with different doses of artemisinin and incubated for 48 and 72 h. A set of untreated control cells was also incubated for the same time. The untreated control and artemisinin-treated samples were measured in triplicates (Hu et al, 2014). Three wells of medium alone were included to provide the blanks for absorbance readings.…”

Section: In Vitro Cytotoxicity Testmentioning

confidence: 99%

Artemisinin Represses Telomerase Subunits and Induces Apoptosis in HPV‐39 Infected Human Cervical Cancer Cells

Mondal

Chatterji

2015

J of Cellular Biochemistry

View full text Add to dashboard Cite

Artemisinin, a plant-derived antimalarial drug with relatively low toxicity on normal cells in humans, has selective anticancer activities in various types of cancers, both in vitro and in vivo. In the present study, we have investigated the anticancer effects of artemisinin in human cervical cancer cells, with special emphasis on its role in inducing apoptosis and repressing cell proliferation by inhibiting the telomerase subunits, ERα which is essential for maintenance of the cervix, and downstream components like VEGF, which is known to activate angiogenesis. Effects of artemisinin on apoptosis of ME-180 cells were measured by flow cytometry, DAPI, and annexin V staining. Expression of genes and proteins related to cell proliferation and apoptosis was quantified both at the transcriptional and translational levels by semi-quantitative RT-PCR and western blot analysis, respectively. Our findings demonstrated that artemisinin significantly downregulated the expression of ERα and its downstream component, VEGF. Antiproliferative activity was also supported by decreased telomerase activity and reduced expression of hTR and hTERT subunits. Additionally, artemisinin reduced the expression of the HPV-39 viral E6 and E7 components. Artemisinin-induced apoptosis was confirmed by FACS, nuclear chromatin condensation, annexin V staining. Increased expression of p53 with concomitant decrease in expression of the p53 inhibitor Mdm2 further supported that artemisinin-induced apoptosis was p53-dependent. The results clearly indicate that artemisinin induces antiproliferative and proapoptotic effects in HPV-39-infected ME-180 cells, and warrants further trial as an effective anticancer drug.

show abstract

“…Dihydroartemisinin (DHA), a main active metabolite of artemisinin (ART), which is making a crucial contribution to the therapy of malaria, 1 has been demonstrated to exert preferentially cytotoxic effects toward various human cancers, including breast cancer, 2 ovarian cancer, 3 cervical cancer 4 and colorectal carcinoma. 5 Recent studies have shown that the anti-cancer activity of ART derivatives including DHA is mainly executed by ironmediated cleavages of endoperoxide bridges.…”

Section: Introductionmentioning

confidence: 99%

p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy

Chen

Zeng

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

Dihydroartemisinin (DHA) exhibits anticancer activities in a variety of cancer cells, but DHA alone are not effective enough for cancer therapy. In this study we found the stress-regulated protein p8 was obviously increased after DHA treatment in several cancer cells, which further to induce autophagy by the upregulation of endoplasmic reticulum stress-related protein ATF4 and CHOP. Furthermore, when we silenced p8 by siRNA in cancer cells, the apoptosis induced by DHA were notably increased, whereas the overexpression of p8 in cancer cells leaded to the resistance to DHA-induced apoptosis. Moreover, we found the inhibition of autophagy with chloroquine (CQ) can enhance the anticancer effect of DHA both in vitro and in vivo. In conclusion, we found that p8-mediated autophagy attenuates DHA-induced apoptosis in cancer cells, which provides evidence to support the use p8 as a cancer therapeutic target, and suggests that the combination treatment with DHA and autophagy inhibitor might be an effective cancer therapeutic strategy.

show abstract

Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2

Cited by 62 publications

References 36 publications

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine

Artemisinin Represses Telomerase Subunits and Induces Apoptosis in HPV‐39 Infected Human Cervical Cancer Cells

p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy

Contact Info

Product

Resources

About