Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo

Xu, Lina; Zhao, Na; Chen, Jinyan; Ye, Piaopiao; Nan, X.; Zhou, Haihong; Jiang, Qiwei; Yang, Yang; Huang, Jingmin; Yuan, Meng-Ling; Xing, Zihao; Wei, Meng-Ning; Yao, Li; Shi, Zhi; Yan, Xiaojian

doi:10.3389/fonc.2019.00002

Cited by 38 publications

(20 citation statements)

References 43 publications

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“…The ethanol was then discarded and cleaned with cold PBS before staining with PI (50 µg/ml) for 15 min before being measured by FCM with an excitation wavelength of 480 nm through an FL-2 filter (585 nm). ModFit LT 3.0 software (Becton Dickinson) was used to quantify the date (29,30).…”

Section: Cell Cycle Assaymentioning

confidence: 99%

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

et al. 2019

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Overexpression of drug efflux transport ABCB1 is correlated with multidrug resistance (MDR) among cancer cells. Upregulation of ABCB1 accounts for the recurrence of resistance to docetaxel therapy in ovarian cancer with poor survival. Erastin is a novel and specific small molecule that targets SLC7A11 to induce ferroptosis. In the present research, we explored the synergistic effect of erastin and docetaxel in ovarian cancer. We confirmed that the co-delivery of erastin with docetaxel significantly decreased cell viability, promoted cell apoptosis, and induced cell cycle arrest at G2/M in ovarian cancer cells with ABCB1 overexpression. Mechanistically, erastin dominantly elevated the intracellular ABCB1 substrate levels by restricting the drug-efflux activity of ABCB1 without alteration of the expression of ABCB1. Consequently, erastin can reverse ABCB1-mediated docetaxel resistance in ovarian cancer, revealing that the combination of erastin and docetaxel may potentially offer an effective administration for chemo-resistant patients suffering from ovarian cancers.

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Section: Cell Cycle Assaymentioning

confidence: 99%

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

et al. 2019

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“…We have also demonstrated that celastrol was able to enhance the sensitivity of the doxorubicin-resistant colon cancer cells via direct binding to P-glycoprotein1 (P-gp), a multidrug resistance protein belonging to ATP-dependent transporters. Interestingly, a few recent reports have indicated that celastrol has the potential to induce intracellular ROS generation in lung, osteosarcoma, melanoma, and ovarian cancer cells [20–23]. This prooxidative activity of celastrol was associated with the induction of cytotoxic effects in these tumors.…”

Section: Introductionmentioning

confidence: 99%

Prooxidative Activity of Celastrol Induces Apoptosis, DNA Damage, and Cell Cycle Arrest in Drug-Resistant Human Colon Cancer Cells

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Szyjka

Paliszkiewicz

et al. 2019

Oxidative Medicine and Cellular Longevity

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Cancer resistance to chemotherapy is closely related to tumor heterogeneity, i.e., the existence of distinct subpopulations of cancer cells in a tumor mass. An important role is assigned to cancer stem cells (CSCs), a small subset of cancer cells with high tumorigenic potential and capacity of self-renewal and differentiation. These properties of CSCs are sustained by the ability of those cells to maintain a low intracellular reactive oxygen species (ROS) levels, via upregulation of ROS scavenging systems. However, the accumulation of ROS over a critical threshold disturbs CSCs—redox homeostasis causing severe cytotoxic consequences. In the present study, we investigated the capacity of celastrol, a natural pentacyclic triterpenoid, to induce the formation of ROS and, consequently, cell death of the colon cancer cells with acquired resistant to cytotoxic drugs (LOVO/DX cell line). LOVO/DX cells express several important stem-like cell features, including a higher frequency of side population (SP) cells, higher expression of multidrug resistant proteins, overexpression of CSC-specific cell surface marker (CD44), increased expression of DNA repair gene (PARP1), and low intracellular ROS level. We found that celastrol, at higher concentrations (above 1 μM), significantly increased ROS amount in LOVO/DX cells at both cytoplasmic and mitochondrial levels. This prooxidant activity was associated with the induction of DNA double-strand breaks (DSBs) and apoptotic/necrotic cell death, as well as with inhibition of cell proliferation by S phase cell cycle arrest. Coincubation with NAC, a ROS scavenger, completely reversed the above effects. In summary, our results provide evidence that celastrol exhibits effective cytotoxic effects via ROS-dependent mechanisms on drug-resistant colon cancer cells. These findings strongly suggest the potential of celastrol to effectively kill cancer stem-like cells, and thus, it is a promising agent to treat severe, resistant to conventional therapy, colon cancers.

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“…Celastrol has an efficient anti-cancer property against several cancer types. In ovarian cancer, apoptosis induced by celastrol is mediated by ROS generation [ 202 ]. Additionally, celastrol hinders gastric cancer growth in vivo by modulating a number of cell-cycle and apoptosis-related genes such as CDKN1B [ 203 ].…”

Section: Oncogenic Mirnas Inhibited By Phytochemicals Currently Evmentioning

confidence: 99%

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

et al. 2020

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Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.

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Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo

Cited by 38 publications

References 43 publications

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Prooxidative Activity of Celastrol Induces Apoptosis, DNA Damage, and Cell Cycle Arrest in Drug-Resistant Human Colon Cancer Cells

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

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