Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

Kumavath, Ranjith; Paul, Sayan; Pavithran, Honey; Paul, Manash K.; Ghosh, Preetam; Barh, Debmalya; Azevedo, Vasco

doi:10.3390/biom11091275

Cited by 39 publications

(25 citation statements)

References 192 publications

(238 reference statements)

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“…Similarly, bactericidal, antiviral, anti‐inflammatory, and wound healing properties of plants are attributed to the presence of tannins (Rajasekar et al, 2021). Glycosides and saponins are known to be effective in management of cardiac diseases and have anticancer as well as immune regulatory potencies (Kumavath et al, 2021). Phenolic compounds are attributed with astringent, antioxidant, antimutagenic, cytotoxic, and antibacterial potentials (Anwar et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Pharmacognostic standardization of Xanthium spinosum L. through scanning electron microscopy and analytical techniques

Shabana

Barkatullah

Nafees

2022

Microscopy Res & Technique

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The present study was intended to evaluate the pharmacognostic attributes including macroscopy, microscopy, physico‐chemical and phytochemical screening of the aerial part of Xanthium spinosum, belonging to family Asteraceae. Morphologically, the leaf was covered with sparsely scattered non‐glandular, multicellular hair on adaxial surface, while abaxial surface was reported with dense silvery furs. Leaf showed lamphystomatic nature bearing anomocytic stomata. Various other leaf constant values like vein islets number, vein termination number and palisade cell ratio were also observed and recorded as 4.36 ± 0.5, 3.36 ± 0.5, and 11.82 ± 2.04, respectively. Cross section of the stem showed typical dicot anatomy differentiated into a single epidermal layer followed by few rows of collenchyma cells, thin‐walled parenchyma cells followed by closed and collateral vascular bundles having prephloemic sheaths and a central pith. Light and scanning electron microscopy of the powdered drug revealed a variety of tissues and cells fragments having different measurements. Fluorescence analysis of the fine powder treated with different reagents revealed a variety of colors implying as a sign for the presence of various biochemical constituents. Highest and lowest percent extractive value was found in methanol and distilled water which were 29.10% and 9.80%, respectively. Qualitative phytochemical screening revealed the presence of various secondary metabolites like flavonoids, phenols, tannins, glycosides, phytosterols, glycosides, saponins, and coumarins, while quantitative phytochemical screening detected maximum quantity of flavonoids in chloroform followed by methanol and ethyl acetate. The aforementioned studies have been reported first time for the said species, which may be helpful for the standardization of the current taxon.

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Section: Discussionmentioning

confidence: 99%

Pharmacognostic standardization of Xanthium spinosum L. through scanning electron microscopy and analytical techniques

Shabana

Barkatullah

Nafees

2022

Microscopy Res & Technique

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“…Proscillaridin A is a plant-derived cardiac glycoside that inhibits Na + /K + -ATPase activity [35]. In addition to its therapeutic effect in cardiovascular diseases, proscillaridin A and other cardiac glycosides have been found to show antitumor effects in various types of cancer [36,37]. Currently, a dozen clinical trials of cardiac glycosides in patients with cancer are underway.…”

Section: Discussionmentioning

confidence: 99%

Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

Semba

Takamatsu

Komazawa-Sakon

et al. 2022

IJMS

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via O-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.

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“…Cardiac glycoside, a class of steroidal glycosides with significant physiological activities, has been reported to possess potent antitumor efficacy and to selectively inhibit the proliferation of human tumor cells [ 6 , 7 ]. Convallatoxin, which can be found in lily of the valley (Convallaria majalis), is a natural cardiac glycoside [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Convallatoxin suppresses osteosarcoma cell proliferation, migration, invasion, and enhances osteogenic differentiation by downregulating parathyroid hormone receptor 1 (PTHR1) expression and inactivating Wnt/β-catenin pathway

et al. 2022

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Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Convallatoxin, a natural cardiac glycoside, exhibits potent anti-tumor activities. Literature has confirmed that PTHR1 is highly expressed in OS tissues and cells and downregulation of PTHR1 could decrease the invasion and growth of OS cells and increase tumor differentiation. In addition, PTHR1 could activate Wnt signaling pathway to promote the malignant functions of OS. In the present study, MG63 and U2OS cells were treated with 0, 12.5, 25, and 50 nM convallatoxin in order to elucidate the precise function of convallatox on the malignant behaviors of OS cells. Moreover, MG63 and U2OS cells treated with convallatoxin were transfected with Ov-PTHR1 or sh-DKK1, aiming to explore whether convallatoxin impeded the malignant progression of OS by modulating PTHR1 and Wnt/β-catenin pathway. CCK-8, wound healing and transwell assays were employed to assess the proliferation, migration, and invasion of OS cells. Differentiation markers (collagen 1, osteopontin, RANKL, Runx2, osteocalcin) were measured to evaluate OS cell differentiation. Results illuminated that convallatoxin suppressed proliferation, migration, and invasion as well as promoted osteogenic differentiation of OS cells. Besides, convallatoxin inhibited PTHR1 expression and inactivated Wnt/β-catenin pathway and PTHR1 overexpression activated Wnt/β-catenin pathway. Furthermore, PTHR1 overexpression or DKK1 knockdown reversed the suppressing effects of convallatoxin on OS cell proliferation, migration, and invasion, as well as the enhancing effect of convallatoxin on OS cell osteogenic differentiation. Collectively, convallatoxin may repress the malignant progression of OS by blocking PTHR1 and Wnt/β-catenin pathway.

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Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

Cited by 39 publications

References 192 publications

Pharmacognostic standardization of Xanthium spinosum L. through scanning electron microscopy and analytical techniques

Pharmacognostic standardization of Xanthium spinosum L. through scanning electron microscopy and analytical techniques

Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

Convallatoxin suppresses osteosarcoma cell proliferation, migration, invasion, and enhances osteogenic differentiation by downregulating parathyroid hormone receptor 1 (PTHR1) expression and inactivating Wnt/β-catenin pathway

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