Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to Doxorubicin

Li, Hanmei; Krstin, Sonja; Wang, Shihui; Wink, Michael

doi:10.3390/molecules23030557

Cited by 74 publications

(41 citation statements)

References 35 publications

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“…Several groups have already studied the cytotoxic effects of piperine, as well as its ability to overcome the MDR phenotype, a multifactorial phenomenon linked to EMT process [45][46][47][48][49]. Given the evidence, it is plausible to infer that piperine may be further used as a prototype molecule for the development of new derivatives with strong anti-carcinogenic effects.…”

Section: Introductionmentioning

confidence: 99%

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

et al. 2020

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Background: Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. Methods: The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. Results: The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. Conclusions: These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.

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Section: Introductionmentioning

confidence: 99%

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

et al. 2020

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“…Black pepper is one of the most common spices consumed by a large number of populations worldwide. Piperine has been reported to enhance the activity of the anticancer drugs in various drug‐resistant cancer cells (Khan, Maryam, Mehmood, Zhang, & Ma, 2015; Li, Krstin, Wang, & Wink, 2018; Manayi, Nabavi, Setzer, & Jafari, 2018; Syed et al., 2017), including colorectal cancer cell line (Bolat et al., 2020). Several effector mechanism of piperine against cancer cell line such as influencing redox homeostatsis, autophagy, cancer stem cell inhibition and endoplasmic reticulum modulation has been postulated earlier (Rather & Bhagat, 2018).…”

Section: Introductionmentioning

confidence: 99%

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

Shaheer

Somashekarappa

Lakshmanan

2020

Journal of Food Science

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Piperine, a bioactive alkaloid, is known to have anticancer activities. Hence, in this study, the effectiveness of piperine pretreatment as a strategy for radio‐sensitizing colorectal adenocarcinoma cell line (HT‐29) was analyzed. For this, HT‐29 cells were pretreated with piperine (12.5 and 25 µg/mL) and exposed to γ‐radiation (1.25 Gy) and analyzed for various effector pathways to elucidate the possible mode of action in comparison to individual treatments. The proliferation efficiency of the cells was analyzed by trypan blue dye exclusion assay and MTT assay. The synergistic effects of the combination treatment were analyzed with compuSyn software. Downstream signaling pathways leading to apoptosis were studied using flowcytometry, immunofluorescence, and immunoblot assays. It was observed that combination treatment arrested HT‐29 cells at G2/M phase nearly 2.8 folds higher than radiation treatment alone, inducing the radio‐resistant cells to undergo apoptosis through mitochondria‐dependent pathway. In addition, activation of caspase‐3 and cleavage of poly(ADP‐ribose) polymerases‐1, the key molecular events in apoptotic signaling, were significantly enhanced. Activation of estrogen receptor beta (ERβ), a nuclear hormone transcription factor promoting tumor suppression represents a novel clinical advance towards management and prevention of cancers. Interestingly, the expression of ERβ was increased in the cells treated with piperine. In conclusion, piperine pretreatment enhances radio‐sensitization in HT‐29 cells by inducing the cells to undergo apoptosis hence, can be used as a classic candidate for colon cancer sensitization towards radiotherapy. Practical Application Piperine induces enhanced radiosensitization of colon cancer cell line (HT‐29) by interfering with the cancer cell line proliferation, DNA damage, and apoptosis.

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“…ATP-TCA test observed MRPs protein could make cell resistant to adriamycin, epirubicin, cisplatin, actinomycin D, colchicine and other drugs. The brief mechanism of that phenomenons is mainly based on the following three aspects: First MRPs as ATP-binding protein, plays an excretory function and protection of tissues and cells, mediated efflux exogenous toxins, which acts as a carrier molecule is an energy-dependent efflux pump outward, chemotherapy drugs can discharge cells, the drug concentration inside the cell targets to reduce [31]. Secondly, MRPs antineoplastic protein may enable it away from the site of action in the redistribution of the cell, resulting in a total concentration of intracellular drug has not yet decreased, but the drug cannot be combined with the target site, causing indirect resistance [32].…”

Section: Discussionmentioning

confidence: 99%

Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation

Sun¹,

Chen²,

Zhou³

et al. 2020

Int. J. Med. Sci.

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Objective: To explore a way to reverse the drug resistance for irradiated CNE-1 human nasopharyngeal carcinoma cells and try to develop a new high efficacy with low toxicity therapeutic approach. Methods: 300 Gy irradiated the CNE-1 human nasopharyngeal carcinoma cells, and then treated with single-agent cisplatin or metformin, or combination of both drugs. MTT assay and FCM were applied to detect cell viability and apoptosis. Western blot and RT-PCR were used to characterize the protein and mRNA expression after various drug administrations. Results: The results presented single-agent metformin was capable of arresting the tumor growth and inducing apoptosis in irradiated CNE-1 cells and also demonstrated a synergy effect with cisplatin. Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells. A pan-MRP inhibitor, probenecid, can resecure cisplatin resistance leading by radiation. Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells. It would be a new therapeutic option to conquer cisplatin resistance for advanced NPC patients after radiotherapy.

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Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to Doxorubicin

Cited by 74 publications

References 35 publications

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation

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