Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported to have the anti-cancer potential with no defined hypothesis or mechanism/s. Henceforth present study was in-quested to validate the effect of alpha linolenic acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic acid was recorded to be 17.55μM against ER+MCF-7 cells. Treatment with alpha linolenic acid was evident for the presence of early and late apoptotic signals along with mitochondrial depolarization, when studied through acridine orange/ethidium bromide and JC-1 staining. Alpha linolenic acid arrested the cell cycle in G2/M phase. Subsequently, the in-vivo efficacy was examined against 7, 12-dimethylbenz anthracene induced carcinogenesis. Treatment with alpha linolenic acid demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count, restoration of the histopathological architecture and loss of tumor micro vessels. Alpha linolenic acid restored the metabolic changes to normal when scrutinized through 1H NMR studies. The immunoblotting and qRT-PCR studies revealed participation of mitochondrial mediated death apoptosis pathway and curtailment of hypoxic microenvironment after treatment with alpha linolenic acid. With all above, it was concluded that alpha linolenic acid mediates mitochondrial apoptosis, curtails hypoxic microenvironment along with inhibition of de novo fatty acid synthesis to impart anticancer effects.

BackgroundMethotrexate (MTX) is recognized as an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. Rutin has been reported to have significant anti-inflammatory, antioxidant along with antiulcer properties. The present study was undertaken to corroborate the effect of rutin against MTX induced intestinal toxicity in experimental animals.MethodSix groups of rats (n = 6) were dosed with normal saline (3 ml/kg,i.p.); MTX (2.5 mg/kg,i.p.); rutin (50 and 100 mg/kg,i.p.); rutin + MTX (50 mg/kg + 2.5 mg/kg,i.p.); rutin + MTX (100 mg/kg + 2.5 mg/kg,i.p.) for seven consecutive days and sacrificed on eighth day. The intestinal contents were scrutinized physiologically (pH, total acidity, free acidity, CMDI), biochemically (TBARS, protein carbonyl, SOD, catalase and GSH) and for immunoregulatory cytokines (IL-2, IL-4 and IL-10).Results and DiscussionThe administration of rutin demonstrated significant protection against intestinal lesions damaged by MTX. The treatment with rutin elicited noticeable inhibition of free acidity (26.20 %), total acidity (22.05 %) and CMDI (1.16 %) in the experimental animals similar to control. In MTX treated toxic group, the levels of oxidative markers and immunoregulatory cytokines significantly increased in comparison to control, which was subsequently restored after rutin treatment. Rutin also demonstrated 75.63, 81.00 and 80.43 % inhibition of cyclooxygenase-1 and 2, and 15-lipoxygenase respectively.ConclusionThe positive modulation of MTX toxicity could be attributed to the free radical scavenging and anti-inflammatory (dual inhibition of arachidonic acid pathways) potential of rutin.

Hypoxia-inducible factor-1alpha (HIF-1α) is a major transcription factor that adapts to low oxygen homeostasis and regulates the expression of several hypoxic genes, which aid in cancer survival and development. It has recently piqued the interest of translational researchers in the disciplines of cancer sciences. Hypoxia triggers an ample adaptive mechanism mediated via the HIF-1α transcriptional domain. Anaerobic glycolysis, angiogenesis, metastasis, and mitophagy are adaptive mechanisms that support tumor survival by promoting oxygen supply and regulating oxygen demand in hypoxic tumor cells. Throughout this pathway, the factor-inhibiting HIF-1α is a negative regulator of HIF-1α leading to its hydroxylation at the C-TAD domain of HIF-1α under normoxia. Thus, hydroxylated HIF-1α is unable to proceed with the transcriptional events due to interference in binding of C-TAD and CBP/p300. From this review, we can hypothesize that remodeling of FIH-1 activity is a unique mechanism that decreases the transcriptional activity of HIF-1α and, as a result, all of its hypoxic consequences. Hence, this review manuscript details the depth of knowledge of FIH-1 on hypoxia-associated cellular and molecular events, a potential strategy for targeting hypoxia-induced malignancies.

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This study was undertaken to investigate the effect of α-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (α-chymotrypsin, 5 mg/kg, p.o.); Group IV (α-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by α-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-κB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. α-chymotrypsin afforded significant protection against the deleterious effects of MNU.