Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paclitaxel stabilizes microtubules with inhibition of mitotic spindle formation and has been found effective in several solid cancers. To test whether paclitaxel could be cytotoxic in human HCC cell lines, we used established HuH-7 and HepG2 cell lines. Changes in cell number, DNA synthesis rates and cell viability were determined. We tested whether paclitaxel-treated cells underwent apoptosis, microtubular reorganization, and cell cycle restriction. Studies also examined whether chemosensitization with verapamil enhanced the antitumor activity of paclitaxel. The cell viability was impaired at greater than 0.01 microM paclitaxel concentrations (LD50, 0.8 microM), with flow cytometry indicating accumulation of cells in G2/M, and immunostaining showing polymerized microtubules with characteristic banding patterns. This G2/M restriction was further characterized by flow cytometry, which revealed cyclin A and cdc2 kinase accumulation in paclitaxel-treated cells. Exposure to paclitaxel decreased [3H]thymidine incorporation into DNA in cells at 24 h but this significantly increased at 72 h, most likely due to DNA repair mechanisms related to cell cycle restriction. The cell death was via both apoptotic and non-apoptotic mechanisms. Finally, co-administration of the chemosensitizer verapamil in doses as little as 1 microM increased the antitumor efficacy of paclitaxel by up to five-fold and changed the LD50 of paclitaxel to 0.1 microM. The findings indicate that paclitaxel is cytotoxic to cultured hepatocellular carcinoma cells. Clinical studies of paclitaxel in patients with hepatocellular carcinoma may help determine additional therapies.
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PMID:Paclitaxel shows cytotoxic activity in human hepatocellular carcinoma cell lines. 1021 48

Given the reported side effects associated with chemotherapy and surgical resection, dietary intervention with omega-3 polyunsaturated fatty acids (PUFAs) has been postulated to be an alterative way to prevent liver cancer progression and metastasis. We studied the effects of an omega-3 PUFA, docahexaenoic acid (DHA) on COX-2 expression and the cell cycle control machinery that co-ordinately regulate the HCC cells growth. Our data showed that DHA (0-200 microM) retarded proliferation of the human metastatic HCC cell line MHCC97L dose-dependently. In addition, inhibition of cyclin A/Cdk2 interfered with S-phase progression further in agreement with the result of bivariate flow cytometric analysis which indicated that DNA synthesis time (Ts) was significantly prolonged by DHA in MHCC97L. The N-myc oncogene, the heat shock proteins Hsp27 and glucose-related protein 78 (GRP78) as well as the antioxidant enzymes superoxide dismutase may play significant roles in the cell cycle control and reduced-proliferation of MHCC97L by DHA. Our data indicated that it is imperative to develop therapeutic strategy with omega-3 PUFA that simultaneously targets COX-2 and other cell cycle regulators in hepatocarcinogenesis. This study provides novel mechanistic insights into the modulation of DHA on human hepatocarcinoma.
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PMID:The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation. 2019 45