Sattu Kamaraj

Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma

One of the focuses in current cancer chemoprevention studies is the search for nontoxic chemopreventive agents that inhibit the initiation of malignant transformation. Cancer biomarkers are quantifiable molecules involved in the physiologic or pathologic events occurring between exposure to carcinogens and the development, progression of cancer. Biomarkers may be the consequence of a continuous process, such as increased cell mass, or a discrete event, such as genetic mutation. Analysis of tumor markers can be used as an indicator of tumor response to therapy. Gallic acid is a naturally available polyphenol, possess strong antioxidant activity with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated the antiproliferative effect of gallic acid during diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in male wistar albino rats. DEN treatment resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, 5′-nucleotidase, bilirubin, alpha-fetoprotein, carcinoembryonic antigen, argyophillic nucleolar organizing regions, and proliferating cell nuclear antigen. Gallic acid treatment significantly attenuated these alterations and decreased the levels of AgNORs and PCNA. These finding suggests that gallic acid is a potent antiproliferative agent against DEN-induced HCC.

Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma

Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer.

Capsaicin modulates pulmonary antioxidant defense system during benzo(a)pyrene-induced lung cancer in Swiss albino mice.

The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body weight) to mice led to a marked increase in oxidative stress indicated by alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase and glucose‐6‐phosphate dehydrogenase) and non‐enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre‐co‐treatment with capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting the antioxidant potential of capsaicin in mitigating the oxidative stress mediated damage produced during benzo(a)pyrene‐induced lung cancer. Copyright

Hesperidin attenuates mitochondrial dysfunction during benzo(a)pyrene‐induced lung carcinogenesis in mice

The present study is designed to assess the mitochondrial status during benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice and to reveal the modulatory effect of hesperidin over it. B(a)P (50 mg/kg body weight)‐induced mitochondrial abnormalities was evident from alterations in mitochondrial lipid peroxides, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase, reduced glutathione, vitamin E, and vitamin C), major tricarboxylic acid (TCA) cycle enzyme activities (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha‐ketoglutarate dehydrogenase), electron transport chain (ETC) complexes activities and ATP levels. Ultrastructural changes in lung mitochondria were also in accord with the above aberrations. Hesperidin (25 mg/kg body weight) supplementation effectively counteracted all the above changes and restored cellular normalcy, indicating its protective role during B(a)P‐induced lung cancer.

Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis.

SummaryLiver cancer is the sixth most common cancer worldwide but because of very poor prognosis, it is the third most common cause of death from cancer. There are currently limited therapeutic regimens available for effective treatment of this cancer. Silymarin is a naturally derived polyphenolic antioxidant, is the active constituent in a widely consumed dietary supplement milk thistle (Silybum marianum) extract. Mast cells play an important role in the inflammatory component of a developing neoplasm; they are also a major source for matrix metalloproteinases (MMPs), which are involved in invasion and angiogenesis. In the present study, we investigated whether dietary supplementation of silymarin has any role in mast cell density (MCD) and in the expressions of MMP-2 and MMP-9 in N-nitrosodiethylamine induced (NDEA) liver cancer in Wistar albino male rats. NDEA administered rats showed increased MCD as revealed by toluidine blue staining along with upregulated expressions of MMP-2 and MMP-9. Silymarin treatment inhibited this increase in MCD and downregulated the expressions of MMP-2 and MMP-9 as revealed by Western blotting and immunohistochemistry. In conclusion, silymarin exerted beneficial effects on liver carcinogenesis by attenuating the recruitment of mast cells and thereby decreased the expressions of MMP-2 and MMP-9.

Beneficial influence of capsaicin on lipid peroxidation, membrane-bound enzymes and glycoprotein profile during experimental lung carcinogenesis

This study was designed to examine the impact of a principal component of hot red peppers and chilli peppers, capsaicin, on alterations in lipid peroxidation, membrane‐bound enzyme profiles and glycoprotein levels during benzo(a)pyrene (BP)‐induced lung cancer in Swiss albino mice. BP (50 mgkg−1) induced deleterious changes that were revealed by alterations in lipid peroxidation, membrane‐bound enzyme (Na+/K+ATPase, Ca2+ATPase and Mg2+ATPase) activity, levels of total protein and protein‐bound carbohydrate components (sialic acid, hexose, hexosamine, hexuronic acid and fucose). Pre‐co‐treatment with capsaicin (10 mgkg−1) restored the detrimental effects induced by BP, indicating its protective role in BP‐induced lung cancer.

Capsaicin provokes apoptosis and restricts benzo(a)pyrene induced lung tumorigenesis in Swiss albino mice.

Capsaicin (CAP), a constituent of red chilli and red pepper is exposed to exert compelling anticarcinogenic effects. In the present study, we examined the anti-tumorigenic potential of CAP on benzo(a)pyrene-induced mice lung tumorigenesis by analyzing the markers of apoptosis. Intraperitoneal administration of CAP (10mg/kg body weight) to Swiss albino mice suppressed the development of lung carcinoma by amending the protein expressions of apoptotic regulators p53, Bcl-2, Bax and caspase-3. The apoptotic-inducing nature of CAP was further confirmed by DNA agarose gel electrophoresis, transmission electron microscopic study and ethidium bromide/acridine orange staining. The results obtained from the present study show that CAP inhibits the development of mice lung carcinogenesis through its ability to induce apoptosis. Our present findings provide the basis for further clinical exploration of CAP as an anti-carcinogenic compound against lung carcinogenesis.

The Anticancer Role of Capsaicin in Experimentallyinduced Lung Carcinogenesis

Objectives: Capsaicin (CAP) is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a) pyrene (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks to induce lung cancer at the end of 14th week. CAP was administrated (10 mg/kg body weight dissolved in olive oil) intraperitoneally. Extracellular matrix components were assayed; Masson’s trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(a)pyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline), elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(a)pyrene along with CAP supplemented animals when compared to benzo(a) pyrene alone supplemented animals. The results of Masson’s trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti- cancer role working against experimentally induced lung carcinogenesis.

Potent antitumor and antineoplastic efficacy of baicalein on benzo(a)pyrene-induced experimental pulmonary tumorigenesis.

Current study aims to evaluate the efficacy of baicalein (BE), a naturally occurring bioactive flavanoid (5,6,7‐trihydroxy‐flavone), at a dose of 12 mg/kg body wt in Swiss albino mice exposed to tobacco‐specific carcinogen benzo(a)pyrene [B(a)P] (50 mg/kg body wt) for its ability to mitigate pulmonary adenoma formation and growth. Under coarse observation, B(a)P‐administered mice, after 16 weeks, developed macroscopically detectable tumors, whereas oral treatment with BE to the lung cancer–induced mice significantly reduced tumor incidence in 16‐week pre‐ and posttreated groups. A detailed histopathological examination of lung was conducted to determine the degree of cancer progression. Incidence of anaplasia, hyperplasia, dysplasia, severe dysplasia, and adenocarcinoma were evident in carcinogen‐administrated group in 6, 10, 12, 14, and 16th weeks, respectively, whereas these anomalies were effectively reduced after pre‐ and posttreatment with BE. In the pretreatment group, BE significantly arrested tumor multiplicity by approximately 65% and tumor load by approximately 88%, while in the posttreatment, the compound significantly reduced the tumor multiplicity by approximately 48% and tumor load by approximately 61%. Further analysis of serum tumor markers like carcinoembryonic antigen, CK 19 fragments (CYFRA 21‐1), and tissue marker enzymes like aryl hydrocarbon hydroxylase, adenosine deaminase, γ‐glutamyl transpeptidase, 5′‐nucleotidase, and lactate dehydrogenase in serum and lung homogenate was carried out to substantiate the anticarcinogenic effect of BE. The overall data from our experiments suggested that BE significantly inhibited pulmonary adenoma formation and growth, thus revealing its potent antitumorigenic effect.

Effect of capsaicin on glucose metabolism studied in experimental lung carcinogenesis

In the present study, we have assessed the chemopreventive effect of capsaicin (CAP) on glucose metabolism with reference to blood glucose and liver glycogen levels, key glycolytic, and gluconeogenic enzymes along with electron transport chain (ETC) complexes during benzo(a)pyrene (B(a)P)-induced lung cancer in Swiss albino mice. B(a)P (50 mg kg−1 body weight)-induced lung cancer animals showed marked decline in blood glucose levels, glycogen levels, elevations in the activities of key glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase), and gluconeogenic enzymes (glucose-6-phosphatase and fructose-6-phosphatase) together with a decrease in the activities of ETC complexes. Supplementation of CAP (10 mg kg−1 body weight) inhibited all the above alterations during lung cancer and restored near normalcy. Histochemical analysis by periodic acid Schiffs staining further confirmed the biochemical findings that highlighted the chemopreventive action of CAP during B(a)P-induced experimental lung tumourigenesis.