A reliable and affordable 3D tumor spheroid model for natural product drug discovery: A case study of curcumin

Tan, Loh Teng‐Hern; Low, Liang Ee; Tang, Siah Ying; Yap, Wei Hsum; Chuah, Lay Hong; Chan, Chim Kei; Lee, Learn‐Han; Goh, Bey Hing

doi:10.36877/pddbs.a0000017

Cited by 15 publications

(11 citation statements)

References 19 publications

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“…The natural products that exhibit pharmacological properties have been harnessed as clinically important drugs to treat diseases. Besides their direct therapeutic use, the fascinating molecular frameworks of natural products offer a range of diverse unique chemotypes as inspiration for the development of current clinically significant drugs or potential novel drugs (Chan, Tan, Chan, Lee, & Goh, ; Nielsen, ; Rodrigues, Reker, Schneider, & Schneider, ; Tan, Low, et al, ). Whereas the natural environment is regarded as a rich source of unique chemical diversity, the reduced trend in the discovery of new bioactive compounds as well as the frequent rediscovery of previously identified compounds have been an increasing challenge for the field of drug discovery from natural products (Lam, ; Li & Vederas, ).…”

Section: Introductionmentioning

confidence: 99%

Streptomyces sp. MUM273b: A mangrove‐derived potential source for antioxidant and UVB radiation protectants

et al. 2019

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Microbial natural products serve as a good source for antioxidants. The mangrove‐derived Streptomyces bacteria have been evidenced to produce antioxidative compounds. This study reports the isolation of Streptomyces sp. MUM273b from mangrove soil that may serve as a promising source of antioxidants and UV‐protective agents. Identification and characterization methods determine that strain MUM273b belongs to the genus Streptomyces. The MUM273b extract exhibits antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging activities and also metal‐chelating activity. The MUM273b extract was also shown to inhibit the production of malondialdehyde in metal‐induced lipid peroxidation. Strong correlation between the antioxidant activities and the total phenolic content of MUM273b extract was shown. In addition, MUM273b extract exhibited cytoprotective effect on the UVB‐induced cell death in HaCaT keratinocytes. Gas chromatography–mass spectrometry analysis detected phenolics, pyrrole, pyrazine, ester, and cyclic dipeptides in MUM273b extract. In summary, Streptomyces MUM273b extract portrays an exciting avenue for future antioxidative drugs and cosmeceuticals development.

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Section: Introductionmentioning

confidence: 99%

Streptomyces sp. MUM273b: A mangrove‐derived potential source for antioxidant and UVB radiation protectants

et al. 2019

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“…Despite of the advancement treatment against malignancy, there has been massive effort and renewed interest in discovering safer yet effective therapeutic candidates especially natural derived-phytochemicals [27][28][29][30][31][32][33][34][35][36][37][38][39][40] . Geraniin, a multifunctional plant-based compound, which is found in various plants and possess multitude of health benefits [41] .…”

Section: Discussionmentioning

confidence: 99%

Targeting apoptosis via inactivation of PI3K/Akt/mTOR signaling pathway involving NF-κB by geraniin in HT-29 human colorectal adenocarcinoma cells

Chan¹,

Tang²,

Goh³

et al. 2019

Prog Drug Discov Biomed Sci

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Dietary phytochemicals possess a variety of biological activities which can be widely discovered in fruits, vegetables and herbs. Geraniin, an ellagitannin is commonly found in fruits and herbs which possesses multitude of health benefits including anti-diabetic, hepatoprotective, anti-inflammatory and anticancer. However, the effects of geraniin on human colorectal adenocarcinoma cells have yet to be evaluated. This study aimed to investigate the apoptotic effects of geraniin against selected human cancer cell lines and elucidate its underlying mechanisms. Geraniin exhibited the strongest cytotoxic effect on HT-29 cells as determined by MTT assay. Events of apoptosis induced by geraniin in HT-29 cells was portrayed by apoptotic morphological changes, externalization of phosphatidylserine, DNA fragmentation and dissipation of mitochondrial membrane potential. Western blot analysis was then used to investigate the mechanisms underlying observed growth inhibition. Geraniin was found to initiate p53 activation further resulting in elevation of Bak/Bcl-xL ratio and caspase-3 activation. This eventually led to HT-29 cell death via apoptosis. Additionally, exposure of geraniin on HT-29 cells found to suppress the PI3K/Akt/mTOR pathway and suppression of NF-kB. Cumulative evidences in this study suggests that geraniin inhibited colorectal adenocarcinoma cell proliferation via apoptosis induction and suppression of PI3K/Akt/mTOR pathway. Thus, these findings provide novel mechanistic insight for the therapeutic potential of geraniin in the treatment of colorectal adenocarcinoma.

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“…Through the ages, a significant number of potential bioactive compounds are from natural sources and these have greatly contributed to many different fields including medicine, cosmetic studies, and agriculture [146][147][148][149][150][151]. As can be seen in Table 2, some of the bioactive compounds reported by various studies are antioxidants and thus are able to inhibit the increase in ROS generated by UVB.…”

Section: Bioactive Compounds From Naturalmentioning

confidence: 99%

Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

Mahendra

Tan

Pusparajah

et al. 2020

Oxidative Medicine and Cellular Longevity

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Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants. Activation of different signaling pathways connected to inflammation, cell cycle arrest, and intrinsic apoptosis was reported as well. Besides that, essential functions like phagocytosis, osmoregulation, and water permeability of RPE cells were also affected. Although the melanin within RPE cells can act as a photoprotectant, this photoprotection decreases with age. Nevertheless, the changes in lens epithelium-derived growth factor (LEDGF) and autophagic activity or application of bioactive compounds from natural products can reverse the detrimental effect of UVB. Additionally, in vivo studies on the whole retina demonstrated that UVB irradiation induces gene and protein level dysregulation, indicating cellular stress and aberrations in the chromosome level. Morphological changes like retinal depigmentation and drusen formation were noted as well which is similar to the etiology of AMD, suggesting the connection of UVB damage with AMD. Therefore, future studies, which include mechanism studies via in vitro or in vivo and other potential bioactive compounds, should be pursued for a better understanding of the involvement of UVB in AMD.

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A reliable and affordable 3D tumor spheroid model for natural product drug discovery: A case study of curcumin

Cited by 15 publications

References 19 publications

Streptomyces sp. MUM273b: A mangrove‐derived potential source for antioxidant and UVB radiation protectants

Streptomyces sp. MUM273b: A mangrove‐derived potential source for antioxidant and UVB radiation protectants

Targeting apoptosis via inactivation of PI3K/Akt/mTOR signaling pathway involving NF-κB by geraniin in HT-29 human colorectal adenocarcinoma cells

Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

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