Realgar, a traditional Chinese medicine, induces apoptosis of HPV16-positive cervical cells through a HPV16 E7-related pathway

Ding, Wencheng; Ji, Tiantian; Xiong, Wei; Tian, Li; Pu, Demin; Liu, Rong

doi:10.2147/dddt.s172525

Cited by 17 publications

(9 citation statements)

References 17 publications

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“…Therefore, the potential for selection bias could be minimized due to the real-world data assessed from the NHI program. Moreover, most previous studies of the utilization of CHM in cervical cancer focused on either the effects of the specific herbs [25][26][27] or formulas 28 in vitro and in vivo. The comprehensive benefits of complementary Chinese herbal medicine use among patients with cervical cancer have rarely been reported.…”

Section: Discussionmentioning

confidence: 99%

Adjunctive Chinese Herbal Medicine Treatment is Associated With an Improved Survival Rate in Patients With Cervical Cancer in Taiwan: A Matched Cohort Study

Wang

Lin

et al. 2021

Integr Cancer Ther

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Background Cervical cancer is one of the most common cancers in Taiwan. Some patients take Chinese herbal medicine (CHM). However, very few current studies have ascertained the usage and efficacy of CHM in patients with cervical cancer. The aim of this study was to investigate the benefits of complementary CHM among patients with cervical cancer in Taiwan. Methods We included the newly diagnosed cervical cancer patients who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 2000 and 2010. The end of follow-up period was December 31, 2011. Patients who were less than 20 years old, had missing information for age, withdrew from the National Health Insurance (NHI) program during the follow-up period, or only received other TCM interventions such as acupuncture or tuina massage were excluded from our study. After performing 1:1 frequency matching by age and index date, we enrolled 7521 patients in both CHM and non-CHM user groups. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. Results According to the Cox hazard ratio model mutually adjusted for CHM use, age, comorbidity, treatment, and chemotherapeutic agents used, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.29, 95%CI = 0.27-0.31). The survival probability was higher for patients in the CHM group. Bai-Hua-She-She-Cao ( Herba Oldenlandiae, synonym Herba Hedyotis diffusae) and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and Chinese herbal formula, respectively. Conclusions Adjunctive CHM may have positive effects of reducing mortality rate and improving the survival probability for cervical cancer patients. Further evidence-based pharmacological investigations and clinical trials are warranted to confirm the findings in our study.

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Section: Discussionmentioning

confidence: 99%

Adjunctive Chinese Herbal Medicine Treatment is Associated With an Improved Survival Rate in Patients With Cervical Cancer in Taiwan: A Matched Cohort Study

Wang

Lin

et al. 2021

Integr Cancer Ther

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“…Realgar and realgar nanoparticles have been demonstrated to inhibit the proliferation of several cancer cell lines, including cancer stem-like cells (CSLCs) in lung cancer ( Chang et al, 2016 ) and HPV16-positive cervical cancer cell line SiHa and HPV16-positive immortalized cervical epithelial cell line S12 ( Ding et al, 2018 ). RQDs had been demonstrated to inhibit cell growth in JEC cells and HepG2 cells with CCK8 assay ( Qin et al, 2015 ; Wang et al, 2015a ; Wang et al, 2015b ).…”

Section: Discussionmentioning

confidence: 99%

Involvement of autophagy in realgar quantum dots (RQDs) inhibition of human endometrial cancer JEC cells

Liu

et al. 2020

PeerJ

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Realgar (As4S4) has been used in traditional Chinese medicines for treatment of malignancies. The poor solubility of As4S4 hampered its clinical applications. Realgar quantum dots (RQDs) were developed to overcome these problems. Previous studies revealed that the RQDs were effective against endometrial cancer JEC cells and hepatocarcinoma HepG2 cells via inducing apoptosis.Apoptosis and autophagy are important programmed cell death pathways leading to anticancer effects. This study further examined effects of RQDs on autophagy, focusing on the formation of the autophagosome in JEC cells. CCK8 assay was used to examine cell proliferation. Flow cytometry was used to analyze cell cycle. Transmission electron microscopy (TEM) was used to examine the autophagy, cells were transfected with pEGFP-C3-MAP1LC3B plasmid to examine effects of RQDs on autophagosome via confocal microscope. Autophagy-related proteins were examined by Western blot. RQDs exhibited cytotoxicity in JEC cells in a concentration- and time- dependent manner. RQDs induced G2 and S phase arrest in JEC cells. RQDs significantly induced autophagy, with the double-membrane and autophagosome-like structures by TEM. The diffused distribution of pEGFP-C3-MAP1LC3B green fluorescence were become the punctuate pattern fluorescence after treatment with RQDs in cells transfected with pEGFP-C3-MAP1LC3B plasmid RQDs increased the expression of autophagyregulatory proteins LC3 I/II, Beclin-1, p62 and Atg12 in a concentration-dependent manner, similar to autophagy induced by serum starvation, except for p62, as induction of p62 is a characteristic of arsenic compounds. Taken together, the present study clearly demonstrated that RQDs can induce autophagy in JEC cells as one of mechanisms of anticancer effects, and indicated that RQDs may be developed as an autophagy inducer.

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“…Tanshinone IIA and Realgar are agents found in Danshen and Xionghuang that exert excellent anti-tumor activity. They possess significant anti-viral activity by repressing HPV oncogenes and inducing apoptosis through a p53-dependent pathway, making them potent therapeutic agents for the prevention and treatment of cervical and other HPV-related cancers ( 24 , 25 ). Besides, Tanshinone IIA was also reported to induce apoptosis of cervical cancer cells via inhibition of glucose metabolism ( 26 ).…”

Section: Novel Agents For Cervical Cancer Treatment At Preclinical Stagementioning

confidence: 99%

An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies

Liu

Wang

et al. 2021

Front. Med.

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As the leading cause of cancer death, cervical cancer ranks fourth for both incidence and mortality. Cervical cancer incidence and mortality rates have reportedly decreased over the last decades thanks to extensive screening and widespread vaccination against human papilloma virus. However, there have been no major improvements concerning platinum-based chemotherapy on the survival of advanced cervical cancer. Thus, novel agents are urgently needed for the improvement of therapeutic effect. With the development of molecular biology and genomics, targeted therapy research has achieved a breakthrough development, including anti-angiogenesis, immune checkpoint inhibitors, and other treatments that are efficient for treatment of cervical cancer. Apoptosis is a crucial process for tumor progression. Drugs directed at inducing tumor-cell apoptosis are regarded as important treatment modalities. Besides, a number of novel compounds synthesized or derived from plants or microorganisms exhibited prominent anti-cancer activity by changing the apoptotic balance in cervical cancer. In this review, we summarized new target therapy drugs ongoing clinical trials that are used for treatment of cervical cancer. Further, we classified novel agents with a focus on improvement of therapeutic effect pre-clinically. To summarize, we also discussed application prospects of the new uses of old drugs and drug combinations, to provide researchers with new ideas for cervical cancer treatment.

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Realgar, a traditional Chinese medicine, induces apoptosis of HPV16-positive cervical cells through a HPV16 E7-related pathway

Cited by 17 publications

References 17 publications

Adjunctive Chinese Herbal Medicine Treatment is Associated With an Improved Survival Rate in Patients With Cervical Cancer in Taiwan: A Matched Cohort Study

Adjunctive Chinese Herbal Medicine Treatment is Associated With an Improved Survival Rate in Patients With Cervical Cancer in Taiwan: A Matched Cohort Study

Involvement of autophagy in realgar quantum dots (RQDs) inhibition of human endometrial cancer JEC cells

An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies

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