A Novel Resveratrol-Arsenic Trioxide Combination Treatment Synergistically Induces Apoptosis of Adriamycin-Selected Drug-Resistant Leukemia K562 Cells

Chen, Jing; Tian, Baoying; Zhou, Cunmin; Sun, Jingjing; Li, Lin; Jin, Shan; Liu, Quanrui; Fu, Siyu; Liu, Huan; Zhang, Zhewen; Li, Caili; Wei, Hulai

doi:10.7150/jca.34506

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…[19] Recent studies suggest that combinations of ROS-generating anticancer agents are useful for the therapy of acute myeloid leukaemia because of the synergic effects of their anti-leukaemia activities. [31,32] Our study showed that citbismine-E acts as a ROS-generating anticancer agent in human myeloid HL-60 cells. The combination of citbismine-E with other anti-leukaemia agents might be a better strategy for enhancing the anticancer activity of citbismine-E.…”

Section: Resultsmentioning

confidence: 78%

Cytotoxic activity of dimeric acridone alkaloids derived from Citrus plants towards human leukaemia HL-60 cells

Murata

Kohno

Ogawa

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Acridone alkaloids from Citrus and their derivatives show various kinds of biological activity. However, the anticancer activities of dimeric acridone alkaloids with unique structures and the molecular mechanism of these effects are poorly understood. Methods We investigated the cytotoxicity effects of dimeric acridone alkaloids isolated from Marsh grapefruit on human myeloid leukaemia HL‐60 cells. Key findings Of the six dimeric acridone alkaloids tested, citbismine‐E, the most potent, dose‐ and time‐dependently decreased HL‐60 cell viability by inducing apoptosis. The treatment of HL‐60 cells with citbismine‐E yielded a significant increase in levels of intracellular reactive oxygen species (ROS). Citbismine‐E lowered the mitochondrial membrane potential and increased the activities of caspase‐9 and ‐3. In addition, citbismine‐E‐induced apoptosis, decrease in mitochondrial membrane potential and caspase activation were significantly alleviated by pretreatment of the cells with antioxidant N‐acetylcysteine (NAC). Citbismine‐E induced intrinsic caspase‐dependent apoptosis through ROS‐mediated c‐Jun N‐terminal kinase activation. Citbismine‐E‐induced production of oxidative stress biomarkers, malondialdehyde and 8‐hydroxy‐2′‐deoxyguanosine was also attenuated by pretreatment with NAC. Conclusions Citbismine‐E is a powerful cytotoxic agent against HL‐60 cells that acts by inducing mitochondrial dysfunction‐mediated apoptosis through ROS‐dependent JNK activation. Citbismine‐E also induced oxidative stress damage via ROS‐mediated lipid peroxidation and DNA damage in HL‐60 cells.

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Section: Resultsmentioning

confidence: 78%

Cytotoxic activity of dimeric acridone alkaloids derived from Citrus plants towards human leukaemia HL-60 cells

Murata

Kohno

Ogawa

et al. 2020

Journal of Pharmacy and Pharmacology

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“…RSV has been shown to aid the apoptosis of human BC cells without harming healthy cells [18,27,28]. In the current study, RSV had a synergistic inhibitory effect with ATO on MCF-7 cells, but also potentially diminished the toxicity of ATO [20,22]. In the present study, ATO (0-16 μM) alone or combined with RSV (0-100 μM) was used.…”

Section: Discussionmentioning

confidence: 75%

“…In addition, RSV was shown to be safe in healthy volunteers in one clinical trial [19]. Furthermore, RSV has been found to inhibit the proliferation and promote the apoptosis of tumor cells induced by ATO and protect healthy cells against the toxicity wrought by ATO [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Effects of combination treatment using arsenic trioxide and resveratrol on human breast cancer (MCF-7) cells

Zhu

Zhang

et al. 2022

Preprint

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Background: Arsenic trioxide (ATO) has shown remarkable efficacy in the treatment of cancer. Resveratrol (RSV) has anti-tumor, anti-aging, and anti-inflammatory properties. We examined the anti-cancer effects of using ATO plus RSV together against human breast cancer (MCF-7) cells.Methods: MCF-7 cells were treated with ATO (0–16 μM) alone or combined with RSV (0–100 μM). Cell viability and percent apoptosis were estimated using Cell Counting Kit-8, the TUNEL assay and microscopy. mRNA and protein expression of caspase-3, caspase-7, Bax, and B-cell lymphoma (Bcl)-2 were assessed by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Chromatin immunoprecipitation (ChIP) was adopted to determine the histone acetylation of the promoter regions of caspase-3, caspase-7, Bax, and Bcl-2.Results: Combined treatment was more efficacious than treatment of ATO alone or RSV alone in suppressing the viability of MCF-7 cells. The intracellular mechanisms of cytotoxicity of ATO+RSV treatment were revealed to be a relative increase in mRNA and protein expression of caspase-3, caspase-7, and Bax, and relative decrease in Bcl-2, in MCF-7 cells. ChIP results showed that combined treatment increased the acetylation of histone H3K27 in the promoter region of caspase-3, caspase-7, and Bax, but decreased the acetylation of histone H3K27 in Bcl-2.Conclusion: Combination therapy using ATO and RSV could be employed for BC treatment.

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“…ATO has recently been used widely for the treatment of hematologic tumors and a variety of solid tumors, with good results [26,27,37,38]. Numerous studies have demonstrated that ATO induces apoptosis in tumor cells, often accompanied by autophagy [39].…”

Section: Discussionmentioning

confidence: 99%

Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells

Chen¹,

Zhou²,

Yi³

et al. 2021

J. Cancer

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Mitochondria are involved in various biological processes including intracellular homeostasis, proliferation, senescence, and death, and mitochondrial mitophagy is closely related to the development and regression of malignant tumors. Recent studies confirmed that the hypoglycemic drug metformin (Met) exerted various antitumor effects, protected neural cells, and improved immunity, while arsenic trioxide (ATO) is an effective chemotherapeutic agent for the clinical treatment of leukemia and various solid tumors. However, the possible combined antitumor effects of Met and ATO and their cellular molecular mechanisms are unclear. We investigated the role of Parkin-mediated mitochondrial mitophagy in the anti-tumor mechanism of Met and ATO by studying the effects of Met and/or ATO on the proliferation and apoptosis of cervical cancer HeLa cells. Both Met and ATO effectively inhibited the proliferative activity of HeLa cells and induced apoptosis by activating Bax and inhibiting Bcl-2. Met and ATO treatment alone or in combination stimulated mitophagosome accumulation in HeLa cells, increased the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and decreased levels of the mitophagic lysosomal substrate protein P62. The mitochondrial membrane potential of HeLa cells also decreased, accompanied by activation of the mitochondrial translocase TOM system and the Pink1/Parkin signaling pathway. These results suggested that Met and/or ATO could induce mitophagy in HeLa cells via the Pink1/Parkin signaling pathway, leading to mitophagic apoptosis and inhibition of tumor cell proliferation. The combination of Met and ATO thus has enhanced antitumor effects, suggesting that this combination has potential clinical applications for the treatment of cervical cancer and other tumors.

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A Novel Resveratrol-Arsenic Trioxide Combination Treatment Synergistically Induces Apoptosis of Adriamycin-Selected Drug-Resistant Leukemia K562 Cells

Cited by 10 publications

References 30 publications

Cytotoxic activity of dimeric acridone alkaloids derived from Citrus plants towards human leukaemia HL-60 cells

Cytotoxic activity of dimeric acridone alkaloids derived from Citrus plants towards human leukaemia HL-60 cells

Effects of combination treatment using arsenic trioxide and resveratrol on human breast cancer (MCF-7) cells

Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells

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