Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation

Jafri, Asif; Siddiqui, Sahabjada; Rais, Juhi; Ahmad, Sultan; Kumar, Sudhir; Jafar, Tabrez; Afzal, Mohammad; Ali, Arshad

doi:10.17179/excli2018-1928

Cited by 25 publications

(16 citation statements)

References 25 publications

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“…In line with the initial study finding that PGV-1 triggers cell cycle arrest in the G2/M phase (2) and, more specifically, in premetaphase (3). It is also in line with piperine which causes cell cycle termination at more varied phases, namely G0/G1 in 4T1 cells and G2/M in HeLa cells (8,40).…”

Section: Dna Damage Caused By Genotoxic Agents Activatessupporting

confidence: 87%

Piperine Increases Pentagamavunon-1 Anti-cancer Activity on 4T1 Breast Cancer Through Mitotic Catastrophe Mechanism and Senescence with Sharing Targeting on Mitotic Regulatory Proteins

Endah¹,

Wulandari²,

Putri³

et al. 2022

Iran J Pharm Res

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: Pentagamavunon-1 performs more potent anti-cancer effects than curcumin against various cancer cells, but it remains to be optimized. Piperine shows the activity as an enhancer of a therapeutic agent. This study expects to achieve higher effectiveness of PGV-1 on 4T1 breast cancer cells through co-treatment with piperine with exploring the effect of cytotoxicity, mitotic catastrophe, cellular senescence, and target proteins of PGV-1 and piperine on the regulation of mitosis in TNBC cells (4T1). The assays emphasize MTT assay, May Grünwald-Giemsa staining, SA-β-galactosidase assay, and bioinformatics analysis, respectively, to elicit the respected activities. The results revealed that PGV-1 performed a cytotoxic effect with an IC50 value of 9 µM while piperine showed a lower cytotoxic effect with an IC50 value of 800 µM on 4T1 cells 24 h treatment. However, the combination treatment of both showed a synergistic cytotoxic enhancement effect with an average CI value < 1. Furthermore, the combination of PGV-1 and piperine induced mitotic catastrophe and senescence better than the single treatment. Treatment of 1 µM of PGV-1 and 400 µM of piperine increased the percentage of senescent cells by 33%. Bioinformatics analysis revealed that PGV-1 and piperine target proteins play a role in mitotic regulation, namely CDK1, KIF11, AURKA, AURKB, and PLK1, to contribute to mitotic catastrophe. Therefore, piperine increases the effectiveness of PGV-1 to suppress 4T1 cells growth synergistically that may occur through mitotic catastrophe and senescence targeting on mitotic regulatory proteins.

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Section: Dna Damage Caused By Genotoxic Agents Activatessupporting

confidence: 87%

Piperine Increases Pentagamavunon-1 Anti-cancer Activity on 4T1 Breast Cancer Through Mitotic Catastrophe Mechanism and Senescence with Sharing Targeting on Mitotic Regulatory Proteins

Endah¹,

Wulandari²,

Putri³

et al. 2022

Iran J Pharm Res

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“…Endowed with anti-cancer activities, it has been tested against HPV models as well. In HeLa cells, it was demonstrated to induce dose-dependent apoptosis through caspase-3, DNA fragmentation, ROS generation, and nuclear condensation [ 136 ].…”

Section: Purified Phytochemicalsmentioning

confidence: 99%

Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review

Massa

Pagliarello

Paolini³

et al. 2022

JCM

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Human papillomavirus (HPV) still represents an important threat to health worldwide. Better therapy in terms of further improvement of outcomes and attenuation of related side-effects is desirable. The pharmaceutical industry has always targeted natural substances—phytochemicals in particular—to identify lead compounds to be clinically validated and industrially produced as antiviral and anticancer drugs. In the field of HPV, numerous naturally occurring bioactives and dietary phytochemicals have been investigated as potentially valuable in vitro and in vivo. Interference with several pathways and improvement of the efficacy of chemotherapeutic agents have been demonstrated. Notably, some clinical trials have been conducted. Despite being endowed with general safety, these natural substances are in urgent need of further assessment to foresee their clinical exploitation. This review summarizes the basic research efforts conducted so far in the study of anti-HPV properties of bio-actives with insights into their mechanisms of action and highlights the variety of their natural origin in order to provide comprehensive mapping throughout the different sources. The clinical studies available are reported, as well, to highlight the need of uniformity and consistency of studies in the future to select those natural compounds that may be suited to clinical application.

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“…4 There is a variety of natural plant-based bioactive compounds, and their derivatives present sustaining potential anticancer properties. The flavonoids are polyphenolic agents possessing beneficial anticancer effects, such as their role in modulating ROS 5 (reactive oxygen species), which helps in scavenging enzymatic activities, cell cycle arrest, inhibition of cell proliferation, and inducing apoptosis. Flavonoid is a potent antioxidant with a dual activity that triggers antiapoptotic pathways or suppresses downregulation by initiating proinflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

“…19 As a chemotherapeutic molecule, it can modulate oxidative stress and thus shows cytotoxic and antimetastatic properties towards cancer cells. 15,20,5 A toxicity evaluation of Pip showed that a 1.12 mg/kg dose concentration has no adverse effects in Swiss male mice, 21 but a dose concentration more than that was able to create a depression in the central nervous system and reproductive toxicity. 22,23 Moreover, the immunological toxicity potential of Pip should be considered before its application as a therapeutic agent.…”

Section: Introductionmentioning

confidence: 99%

“…Pip is also reported to have antiparasitic, antimicrobial, anti-inflammatory (due to inhibition of the NF-κB pathway), − antidepressant, , and anti-angiogenic properties . As a chemotherapeutic molecule, it can modulate oxidative stress and thus shows cytotoxic and antimetastatic properties towards cancer cells. ,, A toxicity evaluation of Pip showed that a 1.12 mg/kg dose concentration has no adverse effects in Swiss male mice, but a dose concentration more than that was able to create a depression in the central nervous system and reproductive toxicity. , …”

Section: Introductionmentioning

confidence: 99%

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Piperine-Loaded PLGA Nanoparticles as Cancer Drug Carriers

Kaur

Singh

Khan

et al. 2021

ACS Appl. Nano Mater.

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Factors like oxidative stress, environmental risk factors, genetics, chemical treatments, and resistance to treatment strategies all have serious impediments in scientific progress for treating diseases. Naturally occurring bioactive compounds when associated with nanocarriers could provide a solution for tackling problems as therapeutic agents against cancer. This report investigates a facile method of using ultrasonic atomization for synthesizing piperine-loaded poly(D,L-lactide-co-glycolic acid) (PLGA) nanocomposites specialized for targeted drug delivery for their potential use against cancer. The nanoformulation was characterized using dynamic light scattering (DLS), microscopic techniques like scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal laser scanning microscopy (CLSM), spectroscopic methods for determination of encapsulation efficiency, sustained-release kinetics, and cellular studies like cellular uptake study and in vitro antitumor activity against different cancer cell lines. The ultrasonic atomization led to the formation of NPs with a mean size of 95 ± 10 nm and a zeta (ζ) potential of −19.29 mV. In vitro release was sustained up to 312 h with about 28% cumulative release at pH 7.2 and 91% at pH 5.5. The tailored delivery of nanocarriers suppressed cancer cell growth and migration in a variety of cancer cell lines, indicating anticancer properties. This nanocarrier formulation showed low cytotoxicity towards HEK-293 in comparison to HeLa, A549, HT1080, PC-3, and MCF-7 cancer cell lines when analyzed for cell viability through 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide dye (MTT) assay. The results suggest that nanocarrier-mediated delivery of piperine (Pip) could prove to be efficient against cancer and aid in reaching inaccessible sites, overcome physiological barriers, and maintain the concentration of drugs, and has higher targeting capability and reduced cellular toxicity.

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Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation

Cited by 25 publications

References 25 publications

Piperine Increases Pentagamavunon-1 Anti-cancer Activity on 4T1 Breast Cancer Through Mitotic Catastrophe Mechanism and Senescence with Sharing Targeting on Mitotic Regulatory Proteins

Piperine Increases Pentagamavunon-1 Anti-cancer Activity on 4T1 Breast Cancer Through Mitotic Catastrophe Mechanism and Senescence with Sharing Targeting on Mitotic Regulatory Proteins

Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review

Piperine-Loaded PLGA Nanoparticles as Cancer Drug Carriers

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