Emerging role of plumbagin: Cytotoxic potential and pharmaceutical relevance towards cancer therapy

Tripathi, Surya Kant; Panda, Munmun; Biswal, Bijesh K.

doi:10.1016/j.fct.2019.01.018

Cited by 102 publications

(89 citation statements)

References 103 publications

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“…Increasing the Production of Intracellular ROS. ROS production is associated with PLB-mediated anticancer effects [9]. To verify the effect of PLB on ROS in TSCC cells, the ROS scavenger NAC was used in our experiment.…”

Section: Plb Inhibits the Viability And Growth Of Tscc Cells Bymentioning

confidence: 99%

“…Plumbagin (5-hydroxy-2-methyl-1,4naphthoquinone, PLB) is a yellow crystalline phytochemical isolated from the roots of plant Plumbago zeylanica L. [8]. It exhibits anticancer effects in human cancers by modulating several molecular mechanisms including autophagy, apoptosis, cell cycle arrest, and generation of reactive oxygen species (ROS) [9,10]. Our previous studies found that PLB has a significant inhibitory effect on the proliferation of TSCC in vitro and in vivo and induces the production of ROS in TSCC SCC25 cell line [ 11,12].…”

Section: Introductionmentioning

confidence: 99%

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Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Xue

Pan

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.

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Section: Plb Inhibits the Viability And Growth Of Tscc Cells Bymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Xue

Pan

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Plumbagin ( Figure 1A) is a naturally occurring 1,4-naphthoquinone and analogue of vitamin K3 isolated from plants of the Plumbaginaceae, Droseraceae, and Ebenaceae families. [1,2] Purified plumbagin inhibits the proliferation of various types of cancer cells, as reviewed extensively in, [3,4] therefore it is considered a valid oncology drug candidate. In vivo studies have shown that it reduces primary tumor burden across cancer types as measured by tumor growth rate as well as tumor weight and volume.…”

Section: Introductionmentioning

confidence: 99%

“…In vivo studies have shown that it reduces primary tumor burden across cancer types as measured by tumor growth rate as well as tumor weight and volume. [4] Plumbagin inhibits the growth of metastatic foci and delays or suppresses metastatic colonization in mouse models of breast cancer, [5] prostate cancer [6] and lung cancer. [7] In addition, the drug appears to improve the efficacy of radiation therapy and of various modalities of chemotherapy in several types of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…[7] In addition, the drug appears to improve the efficacy of radiation therapy and of various modalities of chemotherapy in several types of cancer. [4] If these effects are validated, plumbagin could become a useful adjunct to current standard therapy in a variety of settings. In prostate cancer for example, plumbagin was most effective in combination with androgen deprivation therapy, which is the clinical standard of care for hormone-dependent prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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Plumbagin‐Serum Albumin Interaction: Spectral, Electrochemical, Structure‐Binding Analysis, Antiproliferative and Cell Signaling Aspects with Implications for Anticancer Therapy

et al. 2020

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Plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone) is a small molecule with potent anticancer activity. Like other 1,4‐naphthoquinones, it exhibits electrophilic reactivity towards biological nucleophiles. We demonstrate that plumbagin and structurally related 1,4‐naphthoquinones with at least one unsubstituted quinoid carbon (C2 or C3) bind to albumin, an ubiquitously present nucleophile, with minimum recovery of free drug. Extraction recovery of plumbagin from albumin in solution showed one‐phase exponential decline with a half‐live of 9.3 min at 10 μmol/L. In the presence of albumin, plumbagin exhibited instant changes in UV/Vis absorption bands. Electrochemical analysis using cyclic voltammetry showed a decrease in redox peak currents over time until electro‐inactivity, thus suggesting the formation of a supramolecular adduct inaccessible for electron transfer. The adduct inhibited cell growth and caused cell‐cycle arrest of prostate cancer cells, in part by decreasing levels of the cell‐cycle regulator RBBP. The conjugate displayed similar cellular effects to those described for plumbagin, such as decreased levels of androgen receptor and protein kinase C epsilon. The effect of plumbagin‐albumin on cancer cells was species‐specific, suggesting a receptor‐mediated mechanism. Furthermore, it was blocked by cathepsin inhibitor pepstatin A, indicating that lysosomal degradation is involved in the processing of plumbagin‐albumin adduct. The spontaneously formed adduct of plumbagin with serum albumin is likely to mediate the biological activities of plumbagin in vivo and to fundamentally influence its pharmacodynamics.

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Vitamin K: A novel cancer chemosensitizer

Gul

Maqbool

Maryam

et al. 2022

Biotech and App Biochem

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Cancer incidences are growing rapidly and causing millions of deaths globally.Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, costeffective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.

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Emerging role of plumbagin: Cytotoxic potential and pharmaceutical relevance towards cancer therapy

Cited by 102 publications

References 103 publications

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Plumbagin‐Serum Albumin Interaction: Spectral, Electrochemical, Structure‐Binding Analysis, Antiproliferative and Cell Signaling Aspects with Implications for Anticancer Therapy

Vitamin K: A novel cancer chemosensitizer

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