Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

Lal, Mitu; Gupta, Damodar

doi:10.15190/d.2016.3

Cited by 6 publications

(5 citation statements)

References 28 publications

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“…Expression of SOD I (Cu/ZnSOD) and SOD II (MnSOD) was measured by immune-blotting technique 24 h post treatment as described by Gupta et al with minor modifications. To assess the role of stress responsive pathways, the phosphorylation of JNK and p38 was also measured following various treatments at different time intervals [ 27 , 41 , 46 ]. Briefly, logarithmically growing NKE parental as well as rho zero cells were treated with mannan and/ or exposed to γ-radiation.…”

Section: Methodsmentioning

confidence: 99%

Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells

Sanguri

Gupta

2018

BMC Cell Biol

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BackgroundLow LET Ionizing radiation is known to alter intracellular redox balance by inducing free radical generation, which may cause oxidative modification of various cellular biomolecules. The extent of biomolecule-modifications/ damages and changes in vital processes (viz. cellular homeostasis, inter−/intra-cellular signaling, mitochondrial physiology/dynamics antioxidant defence systems) are crucial which in turn determine fate of cells.ResultsIn the present study, we expended TLR expressing (normal/ transformed) and TLR null cells; and we have shown that mannan pretreatment in TLR expressing normal cells offers survival advantage against lethal doses of ionizing radiation. On the contrary, mannan pretreatment does not offer any protection against radiation to TLR null cells, NKE ρ° cells and transformed cells. In normal cells, abrupt decrease in mitochondrial membrane potential and endogenous ROS levels occurs following treatment with mannan. We intend to irradiate mannan-pretreated cells at a specific stage of perturbed mitochondrial functioning and ROS levels to comprehend if mannan pretreatment offers any survival advantage against radiation exposure to cells. Interestingly, pre-irradiation treatment of cells with mannan activates NFκB, p38 and JNK, alters mitochondrial physiology, increases expression of Cu/ZnSOD and MnSOD, minimizes oxidation of mitochondrial phospholipids and offers survival advantage in comparison to irradiated group, in TLR expressing normal cells.ConclusionThe study demonstrates that TLR and mitochondrial ETC functions are inevitable in radio-protective efficacy exhibited by mannan.

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Section: Methodsmentioning

confidence: 99%

Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells

Sanguri

Gupta

2018

BMC Cell Biol

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“…341 Silymarin induced proteasomal degradation of cyclin D1 and inhibited growth of colon cancer cells. 2016 342 Treatment with silymarin increased the efficacy of ionizing radiation on colon cancer cells causing increased cell death. 2017 343 Silibinin inhibited proliferation and increased apoptosis in colon cancer cells.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

Koltai¹,

Fliegel

2022

J Evid Based Complementary Altern Med

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The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle—the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness.

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“…Irradiation of cells were done using Bhabhatron-II Telecobalt unit (Bhabha Atomic Research Centre, Mumbai, India) 60 Co (dose rate 2.25-2.55Gy/min) at ambient temperature. Radiation dosimetry of unit was carried out by certified radiation safety officer in the institute and Baldwin Farmer secondary dosimeter and Fricke's chemical dosimeter methodologies were used for same [19].…”

Section: Gamma Irradiation Of Cellsmentioning

confidence: 99%

“…Logarithmically growing HCT-15 and RKO cells (approx. 1x10 6 ) were treated with silymarin 20 µg/ml (30 min pretreatment in case of silymarin alone group only) followed by radiation (2-2.5Gy) and after (0, 8, 24 and 48 hrs) incubation samples of all four groups (control, silymarin alone, radiation alone and silymarin+radiation) were processed for western blotting as described by [19]. Briefly following various treatment, cells were harvested and washed twice with ice cold PBS and they're after the cells were lysed in RIPA lysis buffer (1mM EGTA, 25mM sodium orthovanadate, 1% sodium deoxycholate, 1M Tris-Cl (7.4), 1.5M NaCl, 1%Triton X-100, 0.5M EDTA, 200mM PMSF, protease inhibitor, phosphatase inhibitor cocktail (Sigma Aldrich, USA), 0.5M sodium fluoride.…”

Section: Western Blottingmentioning

confidence: 99%

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Silymarin Mediates Apoptosis Through Activation of JNK/ERK Signaling Pathway in Human Colon Carcinoma Cells in Response to ( 60 Co) Gamma Radiation

Lal¹,

Khan²,

Gupta³

2022

Act Scie Canbio

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Colon cancer is the third most common neoplasm worldwide and one of the major causes of death. Thus, major objective of present investigation was to identify and assess a natural molecule available in dietary sources which can sensitize colon carcinoma cells following radiation exposure. HCT-15 and RKO cells were pretreated (-30min) with silymarin followed by radiation (2 and 2.5Gy) exposure and samples were collected, analyzed at different time intervals (0-48 hrs in relation to radiation and silymarin + radiation time point respectively). Expression of proteins related to ERK/ JNK and mode of cell death was measured using western blotting (γ-H2AX, PCNA, ERK/JNK). A significant activation of JNK was observed in both the cells after treatment with silymarin and radiation. In all the samples effect was higher than silymarin alone and radiation with respect to combination group. An increase in apoptosis with increase in DNA damage was found to be accompanied with decreased SOD2 levels (0-48 hr) by combination treated group. In present investigation, silymarin was found to be potent inducer of cell death through ERK/JNK pathway. Silymarin was found to sensitize cells to radiation at non-toxic concentration and sub lethal radiation dose. Silymarin is already being utilized in traditional system of medicine (homeopathy, ayurveda and Chinese system of medicine) and therefore it possesses potential utility in future for treatment of colon cancer.

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Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

Cited by 6 publications

References 28 publications

Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells

Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells

Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

Silymarin Mediates Apoptosis Through Activation of JNK/ERK Signaling Pathway in Human Colon Carcinoma Cells in Response to ( 60 Co) Gamma Radiation

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